THE  SYNTHESIS  OF  ALIPHATIC  ARSENIC  COMPOUNDS  BY 
THE  MEYER  REACTION 

THE  REACTION  BETWEEN  SECONDARY  ARSINES 
AND  ALDEHYDES 

BY 

ARMAND  JAMES  QUICK 

B.  S.  University  of  Wisconsin,  1918 
M.  S.  University  of  Wisconsin,  1919 


THESIS 

Submitted  in  Partial  Fulfillment  of  the  requirements  for  the 

Degree  of 

DOCTOR  OF  PHILOSOPHY 
IN  CHEMISTRY 

IN 

THE  GRADUATE  SCHOOL 

OF  THE 

UNIVERSITY  OF  ILLINOIS 
1921 


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UNIVERSITY  OF  ILLINOIS 


THE  GRADUATE  SCHOOL 


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I HEREBY  RECOMMEND  THAT  THE  THESIS  PREPARED  UNDER  MY 

SUPERVISION  BY-  ArLictnci  Jaiaes  

ENTITLED  TU'E  SYIs  0 UaP S . 

1.,-p^YE^.W  R-RAPTTQu’.  TT.  THE.  RT^IACTIOn  LETWEER  SECQijjJAIiY  AuSIRilj S 
ARD  ALDiihYDES 

BE  ACCEPTED  AS  FULFILLING  THIS  PART  OF  THE  REQUIREMENTS  FOR 
THE  DEGREE  OF 


Recommendation  concurred  in* 


Committee 


Final  Examination* 


Required  for  doctor’s  degree  but  not  for  master’s 


table  0 S’  C 0 L T E H T S 
I THE  SYNTHESIS  OE  ALIPHATIC  ARSElilC  COiiPOUNDS  BY  THE  Ji^EY^JH 
REACTION. 

A.  INTRODUCTION 

1.  The  General  hethode  for  Preparing  Aliphatic 


Arsenicals ■‘- 

2.  The  Meyer  Reaction. 

3*  The  Statement  of  the  Pro'olem.  6 

B.  THEORETICAL ^ 

C.  EXPERIJi/jENTAL 

1.  The  Synthesis  of  Araonic  Acids -i-7 

2.  The  Syiithesis  of  Arsinic  Acids. ^5 

3*  The  Syntheses  of  Arsenic-Substituted  Acetic  Acj.as 

aiid  Derivatives.*  j)l 

D.  ^7 

II  THE  REACTION  BETV/EEN  SECONDARY  ARSINES  . AND  ALDEHYDES. 

A.  THEORETICAL 49 

B.  EXPERIiiflENTAL 

C.  SUi^dvoARY * ^4 

III  MISCELLANESOU  REACTIONS 

A.  THEORETICAL 55 

B.  EXPERIMENTAL 58 


1.  Di-alky larsine  chloride  on  Soaiiuu  it/ialonic  ester.*  58 

2.  Arsines  and  Cnlor o-arsines  on  Diazo-acetic  Ester.  58 
•3»  Phenj'’ larsine  on  the  Grignard  Reagent.  •*••••  60 


C.  SUi/uoARY * 6i 

IV  BIBLIOGRAPHY*  * 62 

V  VITA 63 


Digitized  by  the  Internet  Archive 
in  2015 


https://archive.org/details/synthesisofaliphOOquic 


"^hls  invest ^ati  on  was  undertaken  at  the  susr^estion  of 
Professor  Ko^er  Adams  and  carried  out  un<ier  his  direction. 
The  author  wishes  to  express  his  gratitude  to  him  for  his 
generous  assistance  and  advice  throughout  this  work. 


-1- 


A.  Iiri'RODUCTIOW 

1.  The  General  methods  for  Preparing  Aliphatic  Arsenicals. 

A review  of  the  work  on  the  organic  chemistry  of  arsenic 
strikingly  indicates  the  extensive  development  of  aromatic  ar— 
senicals  as  compared  v/ioh  those  of  the  aliphatic  series.  This 
is  in  part  explained  by  the  fact  that  tne  most  active  and  most 
effective  trypanocidal  drugs  belong  to  the  aromatic  series, 
while  not  a single  aliphatic  arsenic  compouiid  has  beeii  found 
which  possesses  marked  and  definite  therapeutic  properties. 
Aiiother  cause  for  ohis  mibalanced  development  is  found  in  the 
ease  and  convenience  with  which  aromatic  arsenicals  can  oe 
synthesised.  This  is  due  maiiily  to  two  react ioxis:  the 
Bechamp  (1)  which  depends  on  the  direct  arsenatioxi  in  the  para 
positioxi  of  an  aromatic  amine  or  phenol  b3’"  arsexiic  acid  as  illus- 
trated by  the  following  equation: 

CeHeNEa  + HsAs04  = HaHCeHsAsOsEa ( p ) + HaO 

axid  the  Bart  (2  ) which  is  based  on  the  replacemexit  of  axi  aroma- 
tic amino  group  by  the  arsonic  acid  radical  through  the  diazo 
reaction. 

Por  the  aliphatic  series,  on  the  other  hand,  while  the 
mexhods  of  preparation  are  more  numerous,  thej"  are  far  less 
satisfactory.  It  might  be  well  xo  coxisider  briefly  the  most 
important  reactions  and  to  point  out  some  of  their  disadvantages* 
The  oldest  and  historically  the  most  interesting  is  Cadet’s 
reactioii  (3)  wnioh  consists  in  the  dry  distillation  of  an  ixi- 


-2- 


timate  mixture  of  arsenioue  oxide  and  potassium  acetate  oy  wnicn 
a mixture  of  cacodyl  and  cacodyl  oxide  is  obtained.  Trie  method 
is  not  suitaole  for  general  synthesis,  for  not  onl.'V  are  the  pro- 
ducts exceedingly  disagreeable  to  handle  and  very  poisonous,  out 
the  yields  are  poor.  The  method,  moreover,  it  not  applicable 
for  the  preparation  of  the  homologues  of  cacoayl. 

The  second  metnod  which  was  first  applied  by  Landolt  (4) 
for  the  alkylation  of  arsenic  depended  on  the  actioxi  of  an  alkyl 
halide  on  a sodium-arsenic  alloy.  The  disagreeableness  of  hand- 
ling sodium  arsenide,  the  difficult3^  of  controlling  the  reaction 
which  is  very  violent,  and  the  inflammability  of  the  reaction 
products  led  to  the  early  abandojiiment  of  the  method. 

Another  method  ver3r  similar  to  the  preceding  one,  and  reall3 
ail  outcome  of  it,  consists  in  the  interaction  of  aii  alkyl  halide 
and  metallic  arsenic  (5)*  Although  the  method  is  inc oxiveniexit 
because  it  requires  the  use  of  sealed  tubes,  Mannheim  (6),  for 
the  lack  of  a better  methoa  in  his  time,  employed  it  for  the  pre- 
paration of  a xiumber  of  tetra-alkyl  arsonium  iodides.  Tne  use 
of  an  arsenic  amalgam  for  a similar  syxitnesis  is  also  recoraed(7  • 

Of  far  greater  importaxice  than  the  reactions  mexitioned  so 
far  is  the  reaction  of  metallic  alkyls  on  arsenic  halides.  Trie 
zinc  alkyls  were  the  first  to  oe  employed  (8)  but  were  soon  sup- 
erseded 03’’  other  metallic  alkyls,  notaole  mercur\’'  dialkyl  which 
was  first  employed  by  La  Coste  (9)  for  the  synthesis  of  primary 
arsexiic  compouxids.  This  method  caxinot  be  considered  as  a practi- 
cal means  of  syxithes isixxg  primary  and  secondary'  arsexiicals,  for, 
as  pointed  out  b3^  Dehn  (10)  the  mercury  dialkyl  is  difficult  to 


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-5“ 


prepare  and  disagreeable  to  handle,  and  the  product  ootained  is 
difficult  to  free  frora  the  excess  of  reagents  used. 

The  Grignard  reagent  is  the  most  important  metallic  compound 
used  for  the  synthesis  of  tertiary  arsines  (11).  It  is  report- 
ed -that  primary  and  secondary  arsine  halides  are  also  formed  pro- 
vided suitable  proportions  of  reagents  are  used,  but  the  yield 
is  negligible  (12)  . 

All  the  methods  so  far  discussed  witn  the  exception  of  the 
reaction  with  mercury  dialk3^1  lead  to  the  formation  of  tertiary 
arsines  or  to  tetra-alkyl  arsoniuni  halides  if  an  excess  of  alkyl 
halide  is  present.  Hevertneless,  through  the  work  of  Baeyer  ( Ij^ ; 
and  later  others  ( 14 ) a method  was  evolved  for  the  dealkylation 
of  arsines  which  depends  on  the  fact  that  when  an  alkyl  arsenic 
chloride  is  distilled,  alkyl  halide  splits  off  leaving  the  arsine 
with  one  less  alkyl  group.  Thus,  by  the  successive  dealkylation 
a tetra-alkyl  arsonium  halide  can  be  reduced  to  arsenic  triiml- 
ide.  The  following  equations  serve  to  illustrate  the  conversion 
of  an  arsonium  compound  to  a secondary’  arsine  halide. 

R4AsX  + heat  = RsAs  + RX 

RsAs  + Xa  — RgAsXa 

RsAsXa  + heat  = RaAsX  + RX 

While  it  is  thus  possible  to  prepare  primary  and  secondary 
arsines,  it  can  readily  be  seen  that  tne  method  is  much,  too  cum- 
bersome for  general  synthetic  work,  especially  when  large  quan- 
taties  of  luaterials  are  needed. 

Another  metnod  very  sirailar  to  tne  foregoing  methods  is  the 
c ondensat ioii  of  alkyl  halides  with  an  arsenic  t-rihalide  by  means 


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-4- 


of  sodium  for  the' preparation  of  primary,  secondary,  and  ter- 
tiary arsines.  Michaelis  and  Paetow  (15)  were  tne  first  to 
employ  the  method  for  the  preparation  of  aromatic  arsenicals , 
while  Pehn  ( l6 ) extended  it  to  the  aliphatic  series,  preparing 
basic  diisoanyl  arsine  chloride.  The  method  seems  fairly  satis- 
factory for  preparing  secondary  arsines,  but  the  yields  are 
less  than  ^0  per. cent* 

2.  The  Meyer  Reaction. 

A methou  which  is  free  from  most  of  the  objections  of  the 
other  methods  cited,  and  which  offers  the  widest  application  for 
synthesis  in  tne  aliphatic  arseiiical  series  is  the  Meyer  reac- 
tion which  consists  in  the  interaction  of  an  alkyl  halide  with 
sodium  arsenite  to  give  an  alxyl  arsoiiic  acid.  Although  no 
exact  proof  of  the  mechanism  of  the  reaction  has  been  proposed, 
the  follow'ing  structural  equation  is  generally  accepted: 

JOlin  R ^PWa  OWa 

PaOAs^  + RX  NaO-As^  — ^ R-As=0  + NaX 

^OKa  X ^ORa  ONa 

It  can  readily  be  seen  that  the  reaction  is  analogous  to  the  form-:: 

ation  of  aliphatic  sulphonic  acids  from  sodium  sulphite  aiid  an 

alkyl  halide. 

This  reaction  was  first  described  by  G.  keyer  (17)  together 
with  other  similar  ones  which  he  called  anomalous  reactions. 
Klinger  and  Kreutz  ( 18  ) reiiivestigaged  the  reaction  and  improved 
the  method  so  as  to  obviate  the  necessity  of  sealed  tubes.  The 
scope  of  the  reaction  was  considerably  broadeneu  when  Auger  (19) 
found  that  the  alkylation  could  be  carried  on  further  by  allow- 


-5“ 


ing  an  alkyl  iodide  to  react  wiiih  the  sodium  salt  of  aii  alkyl 
arsenious  acid  which  is  prepared  hy  dissolving  axi  alkyl-arsen- 
ious  oxide. in  a calculated  amount  of  sodiu/a  hydroxide.  The 
method  was  again  modified  toy  Be'hn  (10)  for  the  purpose  of  using 
it  in  tone  syiithesis  of  large  amounts  of  ar sonic  acids  ana  x-hen 
used  toy  the  same  author  with  McGrath  (20)  for  the  preparation  of 
two  new  arsonic  acids.  Ihe  method  v/as  employed  oy  Ehrlich  and 
Bertheim  (21)  for  tne  synthesis  of  mixed  arsinic  acids  contain- 
ing one  alkyl  aiid  one  aryl  radical.  In  this  case  the  alxyl 
halide  was  allowed  to  react  with  sodium  phexiylarsenite . Recent- 
ly Burrows  and  Turner  (22)  have  utilized  the  method  for  the  pre- 
paration of  dimethylarsine  iodide,  and  Vaieur  aiid  JDelatoy  (23) 
have  reinvestigated  the  action  of  etnyl  iodide  on  potassium  ar- 
senite. 

The  possitoilities  of  the  iaeyer  reaction  were  recognized  to 
some  extent  in  the  preparation  of  toxic  gases  during  the  recent 
war.  Large  quantities  of  ethylarsonic  acid  from  which  ethyl- 
arsine  dichloride  was  obtained  were  prepared  in  Germany  (24)  toy 
the  action  of  ethyl  chloride  on  sodium  arsenite  under  pressure 
and  at  an  elevated  temperature.  In  this  countrj^  met-hylarsnnic 
acid,  t-he  source  of  methylarsine  dichloride,  was  prepared  toy  the 
action  of  dimethyl  sulfate  on  sodium  arsenite.  (23).  Ija  neither 
case,  however,  was  the  arsonic  acid  isolated. 

Although  the  original  synthesis  has  toeen  modified  at  various 
times,  it  has,  w^i  ch  the  exception  of  the  tvtfo  w^ar  methods,  reiuain- 
ed  fundamentally  unchanged,  and  it  has  retained  its  original  dis- 
advantages. In  the  first  place,  the  use  of  an  alkyl  ioaide  is 


-6- 


ob J ect ioiicible  sine©  it  mo-ices  tbe  isolcitioii  oi  tiie  arsoiiic  a-cid 
exc eedingl3'’  difficult.  Unless  the  iodine  is  removed  before  the 
solution  is  acidified,  the  hydriodic  acid  will  reduce  the  arsen- 
ic acid  immediately.  Of  course,  the  iodine  can  readily  be  re- 
moved by  means  of  silver  nitrate,  but  the  expense  prohibits  its 
use  for  the  preparation  of  large  amouiits  of  material.  The  second 
objection  is  tne  use  of  alcohol  as  a solvent,  for  in  the  alka- 
line media  it  causes  the  formation  of  ethers  to  a considerable 
extent.  Valeur  and  Delaby  (25)  have  found  in  their  study  of 
the  action  of  ethyl  iodide  on  potassium  arsenite,  that  whexi  al- 
cohol was  used  as  solvent  over  ^0  per  cent  of  tne  ethyl  iodide 
was  lost  through  the  formation  of  ether  while  when  it  was  omit- 
ted less  than  10  p er  cent  was  lost,  although  the  conversion  of 
the  potassium  arsenite  in  the  latter  case  was  exceedingly  slovtf. 
Undoubtedly  this  formation  of  ether  becomes  even  more  iiiarked 
with  the  higher  alkyl  halides.  Although  the  two  methods  used 
during  the  war  are  free  from  the  oojections  cited,  they  are  hard- 
ly adapted  for  general  use,  since  one  requires  the  use  of  an 
autoclave,  while  the  other  is  limited  to  the  preparation  of 
methylar sonic  acid. 

3.  The  Statement  of  the  Problem. 

The  brief  review  of  the  jleyer  reaction  clearly  points  out 
the  fact  that  it  is  by  far  the  most  important  and  most  promising 
method  for  the  s3mithesis  of  aliphatic  arsenicals.  Uot  only  is 
it  convenient  and  easy  to  carry  out,  but  it  gives  the  arsonic 
acid  directlj^  from  which  the  other  possible  types  of  arsenicals 


frtrrr»£B 


-7- 


ca.il  DC  prepared*  In  its  present  form  however  it  is  ill  adapted 
for  general  synthetic  work*  The  aim  in  this  work  is  "Do  study  Xp'ne 
reaction  in  order  to  make  it  applicable  to  the  preparation  of  as 
many  t3''pes  of  alipnatic  arsenicals  as  possible,  and  to  help  fill 
the  glaring  gaps  in  t?ie  list  of  this  series  of  compounds.  It 
might  be  well  to  mention  tha^  up  to  the  present  time  only  four 
primary  and  four  secondarj^  arsinic  acids  have  been  prepared,  and 
that  the  exact  constants  for  trimethylarsine  (26)  and  cacodyl 
chloride  (27)  were  not  recorded  until  last  year. 

In  this  work  trie  Meyer  reaction  is  modified  as  follows J the 
alkyl  bromides  are  used  instead  of  the  iodides,  the  use  of  alco- 
hol as  a solvent  is  abandoned,  and  in  its  stead  heating  and  stir- 
ring is  substituted.  With  these  changes  attention  is  first  direc- 
ted to  the  preparation  of  simple  arsonic  acids,  then  extended  to 
diarsonic  acids  and  to  a number  of  special  types  such  as  /^‘-hydroxy 
ethylenearsonic  acid.  The  second  part  of  the  work  is  concerned 
with  the  preparation  of  arsinic  acids,  and  also  a few  special 
types  for  example,  /^-pheno>^ethyl-phenylarsinic  acid,  are  in- 
cluded. The  third  part  of  the  investigation  centers  around  the 
synthesis  of  arsenic-substituted-acetic  acids  of  the  type  RAsOa 
HCHaCOOH,  and  its  derivatives  wriich  are  prepared  by  the  action  of 
cnloroacetic  acid  and  it scderivatives  on  sodium  arylarsenites . 

The  possibility  of  finding  perhaps  some  compounds  of  therapeutic 
value  among  this  series  occasioned  the  preparation  of  the  large 
number  of  derivatives. 


-8- 


B.  THEORETICAL 

In  studying  the  action  of  an  alkyl  oroiiiide  or  chloride  on 
sodium  arseiiite  it  was  found  that  the  most  important  iactors 
were  the  reactivity  of  the  halogen  in  the  alkyl  halide,  the  sol- 
ubility of  the  alkyl  halide,  and  the  temperature  of  the  soaium 
arsenite  solution*  The  effect  of  tne  first  was  clearly  illus- 
trated by  the  great  reactivxiess  of  benzyl  chloride,  as  compared 
with  the  inertness  of  isopropyl  bromide.  A comparison  of  the 
action  of  ethylene  chlorohydrin  and  ethyl  bromide  indicate  the 
effect  of  solubility,  the  former  react iiig  10  times  as  fast  as  the 
latter.  The  best  estiiaate  of  the  method,  however,  can  be  obtaiii- 
ed  by  a study  of  the  synthesis  of  a series  of  arsonic  acids. 

The  first  compound  to  be  prepared  was  the  sodium  salt  of 
methylars Ohio  acid.  No  improvement  over  the  existing  method 
could  be  fouiid,  for,  in  the  first  place,  the  formation  of  ether 
due  to  alcoholic  potash  is  slight,  and  in  second  place,  the  iso- 
lation of  the  acid  in  the  form  of  its  sodium  salt  is  exceedingly 
easy,  since  the  latter  is  iiisoh-ible  in  ^0  per  cent  alcohol.  The 
reaction  does  take  place  in  the  absence  of  alcohol,  but  the 
yields  are  somewhat  lower,  and,  eventually,  alcohol  must  be  added 
to  precipitate  the  product. 

The  advaiitages  of  the  modified  Meyer  synthesis  become  appar- 
ent in  the  preparation  of  ethylarsoiiic  acid.  While  the  formation 
of  ether  is  over  per  cent  v/hen  alcohol  is  used,  no  appreciaole 
amount  of  ether  was  formed  with  the  new  modification.  V/nile  ethyl 
arsonic  acid  was  never  isolated  directly  as  the  free  acid  in  the 


-9- 


old  method  by  either  Dehii  ( l6  ) or  Valeur  (25),  no  difricul&y  was 
experienced  in  doing  that. 

Although  Dehii  obtained  farily  satisfactory  results  in  the 
preparation  of  propylarsonic  acid  ’03''  the  old  method,  ihe  modi- 
fied s3rnthesis  again  proved  superior.  The  3’’ields  v/ere  decidedly 
higher,  and  the  acid  was  readily  obtained  oy  simply  acidifying 
the  reaction  mixture  after  it  had  been  concentrated  to  a small 
volume. 

Although  xi-propyl  bromide  reacted  readily  with  sodium  arsen- 
ite,  isopropyl  bromide  did  not  react,  consequently,  the  arsenic 
acid  could  not  be  prepared.  ]^o  doubt  the  low  boiling  point  of 
the  alkyl  halide  and  the  stabilit3"  of  the  irialogen  atom  are  the 
, main  reasons  for  the  negative  results. 

n-Eutyl  bromide  acted  somewnat  slower  than  n-propyl  oromide, 
but  no  difficulties  were  met  in  trie  preparation  of  large  quanti- 
ties of  the  arsonic  acid.  Due  to  its  relative  insolubility  in 
water  its  isolation  is  exc eedingl3''  simple. 

Although  no  primtiry  or  secondan^  allyl  compound  of  arsenic 
has  previously  been  prepared,  the  preparation  of  allylarsonic 
acid  is  surprisingly  easy.  Whereas  the  preparation  of  simple 
saturated  aJ-iphatic  arsomic  acid  took  about  24  hours,  this  syn- 
thesis was  complete  in  4 hours.  No  trouble  was  experienced  in 
isolating  the  free  acid. 

Ethylene  chlorohydrine  reacted  very  readil3''  with  sodium  ar- 
senite,  but  attempts  to  isolate  the  product  failed.  A syrupy 
liquid  vi/hich  apparently  was  the  impure  compound  since  it  showed 
the  properties  of  an  arsonic  acid,  was  obtained. 


■i.'i 

- - ■ , I 

, , ^ - V.  i ■ . . • ' vi. 

i 

. ( 1 L . V.  - ..  . - . I -k  ' >••’  • >-  • ■ 


jl  s‘'  t . ...  »k  *i  'J  • .J  ' ji.  .'it.  ■•  . 

. . ^,.  ■ s » ' - # A ' » ti  ■ - • -■ 

c . .1  . . ■ } :><  r,  , . 


-10- 

For  unexplainable  reasons  no  appreciable  reactioii  took  place 
vvhen  sodiim  arsenite  was  treated  v-/ith  such  compounds  as  phenr* 
ethyl  bromide,  and  /phenoxypropyl  bromide.  Negative  re- 
sults were  also  obtained  with  et'i'Xjrlene  dibromide,  ana  trimefnyl- 
ene  bromide.  Although  the  latter  reacted,  it  was  not  possiole 
to  isolate  tne  product. 

The  arsonic  acids  are  the  starting  materials  for  the  other 
types  of  compouiids,  as  the  arsines,  the  alkylarsiiie  chlorides, 
and  aikylarsines  oxides.  In  this  work  etriyl  and  n-butylarsine 
dichloride  were  prepared.  The  arsonic  acid  was  dissolved  iii 
concentrated  hydrochloric  acid  t o which  a few  crystals  of  potas- 
sium iodide  hau  been  added,  and  the  solution  saturated  w/ith 
sulphur  dioxide.  The  desired  product  was  obtained  as  an  oil 
which  could  be  purified  by  distillation.  This  method  failed 
with  allyl  arsonic  acid.  An  oil  was  obtained  on  extracting  the 
solution  with  ether,  but  on  atteiripring  to  distil  it^  a tarry 
mass  resulted,  apparently  polymerization  having  taken  place  due 
to  the  unsaturated  linkage. 

Secondary  Arsinic  Acids. 

No  really  satisfactory”  method  is  described  in  the  litera- 
ture for  the  preparatioii  of  secondary  arsinic  acids.  Cadet’s 
reaction  is  limited  to  the  preparation  of  cacodylic  acid,  and, 
furthermore,  it  is  beset  with  experimental  difficulties.  One  of 
the  most  satisfactory  meohods  descrioed  is  -Dne  condensation  of 
an  alkyl  halide  with  arsenious  chloride  'oy  means  of  sodium  using 
molecular  proportions,  nichaelis  and  Paetow  (15)  usiiig  benzyl 
chloride  found  chat  the  secondary  arsine  chloride  pr ed ominaxea . 


-11“ 


Dehn  ( l6  ) used  the  reaction  for  the  preparation  of  di-isoaiuyl- 
arsine  dichloride  which  he  converted  into  the  corresponding  ar— 
sinic  acid  by  the  action  of  bromine  on  the  alkyl- arsine  chloride 
in  aqueous  solution.  In  attempting  to  apply  this  syiithesis  to 
the  preparation  of  di-n-butylars iiiic  acid  results  wnich  were  not 
altogether  satisfactox^^  were  obtained.  The  yield  of  oasic  di- 
n-butyl arsine  chloride  was  never  more  thaxi  ^0  per  cent,  axia  its 
conversion  to  the  arsinic  acid  w'as  far  from  quantitative,  es-pec— 
ially  when  the  directions  of  behti  were  followed,  ixi  which  the 
bromination  was  carriea  out  in  a warm  solutioii.  The  oest  results 
were  obtained  when  the  oromine  was  slowly  addea  to  a well  stirred 
and  cooled  solution,  although  even  thexi  the  yield  was  only  ^0 
per  cent. 

Follov/ing  the  usual  procedure  for  making  arsonic  acids,  the 
Meyer  reaction  was  applied  to  the  syaithesis  of  dialky lar sinic 
acids  with  satisfactory  results.  A sodium  alkylarsenite  was  pre- 
pared by  dissolving  axi  alkylarsixie  dichloride  in  a calculated 
amount  of  10  il.  sodium  hydroxide.  The  reactions  involved  in  the 
synthesis  were: 

RAsCla  + 4NaOH  ->  RAs(  OHa  )a  + 2RaCl 

RAs(0Na)a  + RCl  RaAsOaWa  + RaCl 

The  synthesis  of  the  secondary  arsinic  acids  proceed. s much 
faster  than  that  of  the  arsonic  acids.  Whereas  it  required  about 
24  hours  of  heatiiig  and  stirriiig  to  prepare  the  arsonic  acid, 
only  4 hours  were  required  to  prepare  aixy  of  trie  arsinic  acids. 

In  this  work  diethyl,  di-n-but^^l,  ana  propyloutylars inic  acids 
were  prepared.  Due  to  the  great  solubility  of  diethylarsinic 


i.J  L [ di  ) £U»0C 

..iiVwi 

, . . ...  . L»  / r !•*.  uJ:  ii  L : 

' X *'  * * * * f * A. 

^ . .. . . , i ;.  -Ot^ 


i.u  , . o : 


:*V  .1-  - ‘•-• 


\ ,,  ♦, 


. X-  Ov 


•‘  '^6'^ 


k ' .i.  . > V ._  *'.’• 


1.  . . .V  ■ ! • ‘ 


..V. . ^ ni 


. . >Jt . i 


-12- 


acid,  li  was  difficult  to  get  it  entirely  free  from  traces  of 
sodium  chloride.  lii  tne  case  of  diDutyl  arsinic  acid,  a yield  of 
96  per  cent  was  obtained.  The  great  tendency  of  tne  arsinic  acids 
to  remain  oils  if  impure,  caused  a considerable  aiiiount  of  diffi- 
culty. Although  butyl  bromide  reacted  with  sodium  pheiiylarsenite 
to  the  extent  of  90  per  cent,  no  crystalline  product  ooula  be  ob- 
tained. On  acidifying  the  reaction  mixture,  an  oil  separated 
which  could  not  be  purified. 

Ehrlich  and  Bertheim  (21)  prepared  a number  of  these  alipha- 
tic-aromatic arsinic  acids  by  tne  action  of  an  alkyl  iodide  on  an 
alcoholic  potassium  arsenite  solution.  After  a cedious  and  ex- 
pensive procedure,  which  involved  the  removal  of  the  iodine  by 
means  of  silver  nitrate,  and  the  isolation  of  tne  acias  tnrough 
the  silver  salts,  they  were  obtainea  in  the  form  of  crystalline 
solids. 

Ill  trying  to  prepare  phenyletn^/'iarsinic  acid,  Oiie  of  the 
acids  prepared  by  Bertheim  ana  Ehrlich,  by-  tne  new  metnod  an  oil 
was  also  obtained.  The  oil  possessed  the  chemical  properties  of 
a secondary  arsinic  acid , especially  in  regard  to  soluoility  in 
ammonia  and  alkalies.  If  means  were  found  to  purify  the  product, 
it  would  undoubtedly  be  obtained  in  crystalline  form  witn  yields 
that  would  surpass  those  obtaiiied  by  uhe  older  method. 

In  order  to  get  an  estimate  of  the  scope  of  the  neyer  reac- 
tion a few  special  types  or  arsinic  acids  were  prepared.  /^Pheny- 
oxyet hy 1-phenylarsinic  acid  was  prepared  witn  somewhat  poor  yields 
by  the  action  of  phenoxyethyl  bromide  on  sodium  pherylarsenite. 
An  interesting  di-arsinic  acid  was  prepared  having  the  formula 


I 


) 


I 


\ 

I 


yj  ♦ t.  » • • J 


• i 


I 


k*#«^ 


. J. 


I 


,\ 


4:: 


I 


r 


V"  U' 


i,.. 


ii 


■ap 


-13“ 


CeHBAsOaHCHaCHaAsOaHCfs^  In  trying  to  make  the  corresponding 
t r imet tiylene  diarsinic  acid  an  oil  was  also  obtained  for  which 
no  means  of  purification  were  found. 

Waile  amino  acids  occupy  an  important  position  in  organic 
chemistry,  only  one  arsenic-substituted  aliphatic  acid  is  known. 
This  compound,  which  is  p-amino-phenylarsinic-acetic  acid^was 
prepared  by  Ehrlich  and  Bertheim  (28)  by  the  action  of  chloro- 
acetic  acid  on  sodium  p-amino-phenylarsenite . This  new  exten- 
sion of  the  Meyer  reaction  v^as , however,  noD  developed  further. 

The  derivatives  of  p-amino-phenylarsinic-acetic  acid  as 
well  as  those  of  the  simplier,  phenyl-- arsinic- acetic  acid  are 
interestiiig  oecause  they  represent  a new  type  of  arsenic  com- 
pound which  has  not  oeen  investigated  in  regara  to  its  physio- 
logical properties.  Bixice  a most  thorough  study  has  been  made 
of  arsenicals  in  which  botn  the  arsenic  o,xia  the  xiitrogen  are  at- 
tached airectly  to  the  aromatic  nucleus,  it  seems  advisaole 
to  direct  attentioxi  to  compounds  in  whicn  these  tvxo  elemexits  are 
linked  to  aliphatic  side  chaixis  as  is  the  case  in  the  aromatic- 
substituted  amides  of  these  two  acids. 

These  substances 'possess  properties  wnicn  make  them  adapta- 
ble for  therapeutic  study.  Thej''  dissolve  readily  ixi  sodium  bi- 
carboiiate  to  form  neutral  solutions.  The  arsexiic  is  in  the  sta- 
ble pentavelent  state  wnich  is  desirable  for  preliminary'  biolog- 
ical study.  Due  to  the  simplicity  of  synthesisixig  one  deriva-  . 
tives,  the  parent  substance  can  be  modified  almost  at  will.  The 
extent  to  which  the  modif icatioxis  can  be  carried  out  is  illus- 
trated by  the  compouxid  f'ormed  by  condexisixxg  p-amixio-pnexiylarsen- 


-’1 


, . _ . ^ V , i'l  j . s * - .V  • . ^ . i.  . / i . > '•  . . 

; , I . , . . V,  . ,.1  ■ ■ J.  . tj  .■  i V 1-  - i ^ J. '*iX  • .. 

J 

...........  'i.  . ..i  j j 

■i  i 

..  . ■ ^ .....  ' ^ • .i-.  - 

- - - • ■ ' • > ■ • - - r.  -V  ^ *j 


. . .‘is  V 


^ X..' 


i. 


'*r*' 


i u. .' 


— V*  ^ V 


■ i , t cj  i,  1 it*  v«i  ■X-  < ^ J 


J. 


> I > 


}j  . . 


f 

\ 


: o Lo 


.1 

r 

'i 


; f V 


I 


4 


W 


. ^ J 


t 


% 


i 


i 


, t 


>1 


' 

j 


■-  . •'  V*  ■ 


-14- 


ious  acid  with  chloroacetyl  arsanilic  acid.  It  still  retains  an 
active  amino  group  on  one  end  of  tne  molecule  and  tne  arsonic 
acid  radicle  on  the  other,  while  the  two  aromatic  nuclei  are 
connected  hy  an  ars inic-acetyl-amide  chain* 

Phenyl-arsinic-acetic  acid  was  prepared  oy  the  action  of 
chloroacetic  acid  on  sodium  phenylarsenio e wnicn  was  rnaae  oy 
merely  dissolving  pnenylarsine  dichloride  in  the  calculated 
amount  of  sodium  hydroxide.  By  reducing  the  compouiid  formed 
with  sulphur  dioxide  in  concentrated  hydrochloric  acid  solution, 
pheijyl-bromoarsine-acetic  acid  was  formed,  snowing  that  pheiiyl- 
arsiiiic-acet ic  acid  reacts  as  a secondary  arsinic  acid.  In  order 
to  prepare  derivatives  of  this  acid,  it  was  desirable  to  make 
the  acid-chloride,  but  it  was  soon  found  that  the  reagents  nec- 
essarj-"  to  make  the  latter  c orapound^  split  the  arsenic  radical 
from  the  acetic  acid  group  no  matter  how  carefully  the  conditioxis 
of  the  reaction  were  governed. 

Since  the  acid  ciiloride  could  not  be  prepared,  it  was  xiec- 
essary  to  fixid  some  other  way  to  make  these  acetyl  derivatives. 

It  was  found  thax  Ciiloroacetyl  derivatives,  especially?  lihe  aroma- 
tic substituted  amides  would  react  equally  as  well  as  tne  free 
acid,  giving  directly^  tne  desired  phexiylarsinic  acetyl  derivative 
as  illustrated  oy  tne  follov>?ing  equatioxi: 

CeHBAs(0Pa)3  + ClCE3C0Kim->  CeHeAsOalmCHa COhHR  + RaCl 
The  procedure  was  surprisingly  simple.  A calculated  amount 
of  dhe  chloroacetyl  derivative  was  added  to  a solution  of  sodium 
phenylarsexiit e prepared  in  the  usual  way.  The  desired  reaction 
took  place  without  heatixig  or  stirring,  and  was  generally  com- 


t' 


u - 


. - I 


i fN 


’fi 


...  ^ . .c 

*>.L  - ' " ■’ J J I'*.".. 


. . ..:j . .1 


I ..; 


^ I . _ i.  i i - ••  '■*-  ‘ .j 

<.  * u. . . ' - 

. . . ■ V 

i 4^  .,  Cy  ‘ .»  f .»  C j 

: ; - io 

.*  U /• 


.f  ; ts  • w 

- - ^'• 
■y 


^ ' ‘J  ^• 


4.  .. 


. - r‘  • X - 

^ ^ ; l"*''  *•  ^ 

i';  - .^-,-vAty 

• i . j"r  , . C ..  .ii  •.:{  .<ti/ 


-15- 


piete  in  four  nours.  The  isolation  of  the  product  offered  no 
difficulties.  The  solution  was  xoade  xieutral  to  pneolphthalein 
to  precipitate  the  excess  phenylarsine  oxide,  and  filtered.  On 
acidifying  the  filtrate  until  it  reacted  slightly  acid  to  Congo 
red,  the  product  was  practically  quantitatively  pr.ecipitated . 

The  yield  s varied  considerably,  out  in  some  cases  they  were  as 
high  as  90  per  cent.  At  first  the  reaction  was  carried  out  in 
a 50  cent  alcohol  solution,  but  the  j'^ields  were  considerably 
higher  when  alcohol  was  omitted.  Since  almost  all  of  tne  com- 
rpounds  could  oe  recrystalliksed  from  a large  volume  of  water, 
their  purification  was  relatively'’  easy. 

These  compounas  are  for  the  most  part  slightly  soluole  in 
alcohol  or  glacial  acetic  acid,  but  relatively  ixisoiuble  in  tne 
other  comiuon  solvents.  Tney  melt  fairly  sharply  with  instantan- 
eous decomposition.  All  dissolve  in  sodium  bi-carboiiat e with 
the  evolution  of  caroon  dioxide,  to  give  a neutral  solutioxxs. 

The  possiDility  of  using  these  suostances  to  prepare  cyclic 
compounds  is  illustrated  by  the  fact  that  pnexiylarsinic-acetic 
acid  can  be  reducea  in  the  usual  way  to  phenyl-bromoarsiiie-acet ic 
acid  which  ought  to  yield  a ring  compound  as  illustrated  by  the 
following  equation. 


Lack  of  time  prevexxted  further  developmexit  of  this  work. 


• 'iv 
,;t> 

4 -jC 

V i 4,  4 . 

I . i 


>^4-  -4  -*. 

4-  '-0  < • I 

t-V  L;;i 
4.  .f:y  ; 

^ . • • V. 

...lU  , 

.1 


- .i,  ut-.T  .eCri^L.'oilll* 

-.'1..I  -iitir! a .>•.  f- I'?  uit4  OJ 

:•  i.  j-iJi.W 

..  '.t : .4  0 i itjw  .,r,  jjijo'ivi  &fi!a  »b*i 

. ,4  .V^  '■  b&^TnV 

I . . .vft»o  i9ii  0^  tit4  , 

O'  • .ii4  .j  L‘.  . inr^iOtx-t-  v-'iX^*o  l«q  & 

Ul  4 !'  M w i..  '''^  i.  C i I t..  U Xi»5  .itSf^A’ 

.*4.  t7p  i,..i>4wa 

1'..  -,.  . , 4,  I .•*  .e>^  ..oijiSujL  iXnwq' 

V' 

..o«..  v>w'  1 t4 L>i'\ jOqm' ' t 

J.,u  , Jj,.  ;.  . *4...  j4. -.  '.444j4^.‘*^ia  ’iO  j.OrfiX':'X^i 

r .i  ..  -%.4.i  . .nojJL'Of/ 

'•;i  '.^vi-4*  4 --.  iU.n  .14  4' i ttuo«f 

\ 4,  . 4»j.  i.’i-l.  ^K'J<  iLU  L^ti  ,.*  tulv 

i.iyjJ  .C  -..  ..i.i.Orc4eUH  &£f5‘ 

,.  j ^'0  •■  J I-  c-iJXix  :;i  eixiM'aqaioo 

. ■ ■•i' 

r..  , ■ .,'  .n.^  ‘‘•i  ti  0*lUvT  OvJ  .0 

. ..  i.:  . l -l  r .i;  -.pi1r,Wo 


-16- 


Because  of  the  therapeutic  value  of  arsauiiic  acia,  the  pre^ 
paration  of  a numtoer  of  derivatives  of  p-amino-phenylarsixiic- 
acetic  acid  seemed  advisable.  These  c ompounas  were  prepared  in 
the  same  way  as  those  in  fhe  precediijg  series.  The  cnloroacetyl 
derivatives  were  allowed  i^o  react  witn  tne  sodium  salt  of  p— aiuino 
phenylarsenious  acid  prepared  by  dissolviiig  1 mol-  of  the  Hydro- 
chloride of  p-amino-phenylarsine  dicnloride  in  mols,  of  sodium 
hydroxide.  To  iMike  the  latter  substance,  arsaiiidic  acid  dis- 
solved ixi  concentrated  iij’'drochloric  acid  was  reduced  by  means  of 
sulphur  dioxide.  The  reaction  was  em:irel3'-  similar  to  the  pre- 
cediiig  oiie,  and  the  products  resembled  the  correspond iiig  phenyl- 
arsinic-acetyl  derivatives  in  their  general  physical  and  chem- 
ical properties. 


The  presexice  of  a free  aimlno  group  rendered  the  compounds 
soluble  in  concexit rat ed  hydrochloric  acid,  and  made  the  prepar- 
ation of  N-gylcyl,  and  y-acetyl  derivatives  possible. 

While  the  syntheses  of  aromatic-substituted  amides  proceed- 
ed smoothly  in  all  cases,  the  preparatioxi  of  aliphatic  acetyl 
derivatives  was  attexided  witri  little  success.  The  only  compouxid 
prepared  was  one  calcium  salt  of  p-amino-pnexicy^larsinic -( acid  ) 
acetyl  urea.  Tnese  negative  results  are  uxiuouotedly  explaiiied 
by  the  fact  that  the  speed  of  the  hydrolysis  of  tne  aiipnatic 
acetyl  derivative  exceeds  that  of  the  expected  react!  oxi. 


mm 


-17“ 


C.  EXPERIMEirrAL 

1.  The  Synthesis  of  Arsonic  Acids. 

jt 

Di-Sodiuia  methvlars  onate . 94  g.  of  methyl  iodide_  were  add- 

ed to  a well  stirred  solution  of  60  g.  of  arsenious  oxide  in 
600  cc.  of  2*5  tl  sodium  nydroxide  maintained  at  a temperature 

0 ^ - a.  , - 

of  43-50  • At  the  end  of  30  minutes  an  equal  volume  ol  alconoi 

was  added  to  precipitate  tiie  sodium  salt  of  metnylarsonic  acid. 

After  allowing  tne  solution  10  stanu  several  xiours,  the  product 

was  filtered  off,  v^asded  witn  alcohol,  and  finally  dried  for  one 
^ 0 

hour  at  oO  in  vacuo.  The  yiela  was  100  g.  To  remove  traces 
of  insoluble  impurities,  tne  product  was  redissolved  in  a small 
volume  of  water,  filtered  and  reprecipitated  with  an  almost  quan- 
titative yield  by  the  addition  of  alcohol. 

following  the  directions  of  Klinger  ana  Kreutz,  ( iS ) prac- 
ticall3r  quantitative  yields  were  obtained. 

St hvlar sonic  acid . The  acid  was  prepared  oy  the  action  of 
ethyl  bromide  on  sodium  arsenite.  To  the  sodium  arsenite  pre- 
pared by  dissolving  19S  g arsenious  oxide  in  300  cc.  of  10  N 
sodium  hydroxide,  110  g,  the  theoretical  amount  of  ethyl  bromide^ 
were  added,  but  to  compensate  for  the  loss  due  to  its  volatility 
50“73  §•  more  were  added  in  the  course  of  the  reaction,  ihe 
reaction  v</as  conducted  in  a two-xiecxed  flask  fitted  witn  a re- 
flux condenser  and  a mechanical  stirrer  naving  a mercury  seal. 
After  heating  and  s&irring  tne  mixture  for  24  hours  it  was  found 
that  85  per  cent  of  tne  arsenious  acia  naa  reacted.  To  isolate 
the  product,  the  reaction  mixture  was  concentrated  to  less  than 
* Unpublished  work,  Adams  ana  Jonnson. 


-18- 


one  half  of  its  original  volume  and  filtered  to  remove  the  salt 
which  had  separated  out*  The  filtrate  was  rendered  neutral  to 
phenolphthalein,  again  concentrated,  and  filtered.  It  was  next 
made  acid  to  Congo  red,  again  c oncentrated,  and  filtered  hot.  On 
cooling,  iieedle-like  crystals  togetiier  with  a small  amouiit  of 
sodium  chloride  separated.  By  repeatedly  concentrating  and  fil- 
tering hot,  most  of  the  sodium  chloride  was  removed  and  120  g. 

of  the  product  obtained  which  still  contained  a little  sodium 

o 

chloride.  A sample  carefully  recrystallized  melted  at  . 

La  Coste  found  95^  (29  )>  ana  Dehn  (10),  99»5°» 

In  another  experiment  ethylarsine  dichloride,  itistead  of  the 
acid,  was  isolated.  The  reactiati  mixtuir-e  was  concentrated  and 
acidified  as  before,  but  after  the  solution  had  been  reduced  to 
a small  volume  ^ volumes  of  concentraced  Hydrochloric  acid  were 
added  and  the  precipitated  sodium  chloride  filtered  off.  After 
the  addition  of  a small  amount  of  potassium  iodide  the  solution 
was  saturated  with  sulphur . dioxide  when  the  desired  product  sep- 
arated as  a dark  colored  oil  which  distilled  between  190-I69. 
from  100  g arsenious  oxide,  10^?  g of  produce  were  obtained.  Ex- 
traction of  the  aqueous  layer  with  ether  undoubtedly  would  nave 
increased  the  yield. 

The  reaction  could  readily  be  followed  since  it  ixivolved  the 
conversion  of  tne  arsenic  from  the  trivalexit  to  the  pentavalexit 
state.  At  regular  intervals,  a ^ cc,  sample  was  removed  from 
the  reaction  mixture  and  diluted  to  100  cc . A 9 cc.  portion  of 
this  solution  was  diluted  with  water,  sxightl^/"  acidified,  then 
treated  v;ith  an  excess  sodium  bicarboijate , and  titrated  with  a 


-19- 


standard  iodine  solution. 

n-Proovlarsonic  acid.  Tne  direction  outlined  for  the  prepar- 
ation of  the  preceding  arsonic  acid  were  followed.  To  sodium 
arsenite  ( 9S  g of  arsenious  oxide  dissolved  in  '■^00  cc.  of  10  N 
sodium  hydroxide),  I23  g of  n-propyl  ‘bromide  were  added.  At  t'ne 
end  of  24  hours  65  por  cent  of  fne  sodium  arsenite  had  reacted. 
The  reaction  mixture  was  neutralized  to  phenolphthalein,  concen- 
trated to  approxin:aDely  one-half  its  original  volume,  and  filter- 
ed. The  filtrate  was  rendered  acid  to  Congo  red,  heated  to 
coiling,  and  filtered.  On  cooling  t‘he  desired  product  separated 
in  the  form  of  platelets  together  with  some  arsenious  oxide  and 
sodium  chloride  which  could  readily  be  removed  cy  one  or  two 

recrystaliizat ioiis  from  hoo  water.  A j'-ield  of  100  g.  was  ob- 

0 

tained.  The  melt  hig  poiiit  oi’  a purified  sample  was  123-7  wriich 
agrees  wifn  the  one  recorded  in  the  literature  (l6). 

Isopropvlarsonic  acid.  Althoitgh  tne  same  directions  as 
fhose  used  to  prepare  the  n-proplyarsonic  acid  were  followed,  no 
reaction  'had  taken  place  after  24  hours  oi'  ‘rieating  and  stirring. 

n-ButvlarsQ2iic  acid,  following  the  general  met'nod  already 
outlined  for  the  preparation  of  arsonic  acids,  little  difficulty 
was  experienced  in  the  preparation  of  large  quantities  of  butyl- 
arsonic  acid.  Approximately  3 hg.  of  the  acid  were  made.  A 
typical  run  was  as  follows:  273  g*  of  n-butyl  bromide  were  added 
to  the  sodium  arsenite  prepared  oy  dissolving  196  g.  arsenious 
oxide  dissolved  iii  600  cc.  of  10  M sodium  nydroxide.  ine  mixture 
v;as  heated  on  a water  bath  and  stirred.  Approxiii:ately  30  per 
cent  of  tne  sodium  arsenite  ‘j:iad  reacted  at  tne  ena  of  24  nours 


-20- 


G-iid  70  psr  C62it  cit  "ti'ie  end  of  ^6  nours.  After  steoju  distilxiiig 
off  the  excess  butyl  bromide  and  the  butyl  alcohol  formed  oy  the 
hj^droiysis  of  the  alkyl  halide  by  the  free  alkali/tne  solution 
was  neutralized  to  phenolphtnalein,  concentrated  until  a cmisid- 
erable  amount  of  salt  had  separated  out,  and  filtered.  Oil  acid- 
ifj'-ing,  the  arsonic  acid  separated  in  the  form  of  a thick  crys- 
talline paste  in  almost  quantitative  yields  '^00  g-  of  crude  mat- 
erial containing  about  14  per  cent  arsenious  oxide,  and  some 
sodium  chloride  was  obtaiiied.  The  butj"!  alcohol  ootained  ac- 
counts for  the  butyl  bromide  lost  in  the  reactioti.  The  product 
can  readily  be  purified  by  recrj^'etall ization  from  hot  vmter  in 
which  media  it  is  fairly  soluble,  although  alcohol  is  more 
effective  in  removing  -che  last  traces  of  arsenious  oxide. 

A number  of  experiments  were  carried  out  to  determine  the 
best  conditions  for  tne  reaction.  It  was  found  that  when  sodium 
carbonate  was  used  instead  of  sodium  hydroxide  to  dissolve  tne 
arsenious  oxide,  no  reaction  took  place.  It  was  further  found 
that  the  best  results  were  ootained  when  tne  arsenious  oxide  and 
sodiimi  h3^droxide  were  used  in  ohe  proper  proportions  to  make 
normal  sodium  arsenite.  Practically  no  reaction  took  place  when 
either  more  or  less  sodium  hydroxide  was  used.  The  effect  of 
alcohol  as  solvent  was  also  investigated.  The  usual  procedure 
was  followed  except  in  that  potassium  arsenite  vi/as  used,  and 
that  1 part  of  alcohol  was  added  to  3 parts  of  the  alkali  solu- 
tion. The  reaction  proceeded  until  about  20  per  cent  of  i,he 
potassium  arsCLnite  had  reacted  axia  thexi  stopped  completely. 

n-Butylarsonic  acid  on  recrystallization  is  obtained  as 


-21- 


a flak3'-  crj' stallixie  solid.  In  its  general  oehavior  and  physical 
properties  ii,  resmebles  the  o^her  arsonic  acids.  Oil  boiling 
v;ib  h magnesia  mixture  it  precipitates  a,s  the  magnesium  salt. 
Subs.,  0.2  g,  0.2  g:  21.1,  21.1  cc.  O.IO38  M I. 

Calc,  for  C4EiiAs03*  As,  41,18  0/0  found:  As,  41.2^  0/0 

Jt 

41.23  0/0 

Eutylarsine  dicriloride.  C4HsAsCl3«-  130  g of  crude  n-Out-j’i- 

arsonic  acid  were  dissolved  in  3OO  cc.  of  conceiiorated  ri;y'dro- 

chloric  acid  to  w/iich  a few  crj^'etals  of  potassium  iodide  wnich 

acted  as  a catalyst  nad  been  added.  On  saturating  the  solution 

with  sulphur  dioxide,  100  g.  of  crude  butj’-larsine  dichloride  was 

obtained.  It  v;as  fractionated  twice  under  reduced  pressure  and 

once  under  ordiiiarj'  pressure.  In  this  way  a colorless  highly 

o 

refractive  oil  boiling  at  192—4  was  obtained.  It  is  fairly 
stable  in  water  but  dissolves  readily’-  in  concentrated  alkali. 

In  physiological  properties  it  corresponds  to  the  other  primary 
arsine  chloride,  although  somewhat  less  inarkedlj''  so. 

Subs.  0.5033  g:  0.1756  g.  Cl 

Calc,  for  C4E9ASCI3 : Cl,  ^4*^4*  founded,  ^4*88 

1 a-r  s Q a_ci  d . CsHsAsOaHa  .-Triis  acid  was  prepared  like 

the  precediiig  ones.  23O  g of  allyl  bromide  were  added  to  the 
calculated  amount  of  sodium  arseiiite  (196  g arsenious  oxide  dis- 
solved in  600  cc.  10  N sodium  nj-droxiae  ).  The  reaction  was  66 
per  cent  complete  iii  Oiie  hour  anu  90  par  cent  iii  2 rioui’s.  The 

reaction  mixture  was  neutralized  to  phenolpnthalein,  concentrat- 

• 

^ All  analyses  for  arsenic  were  made  03"  trie  Hooertson's  method.f  20 


I 


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-22- 


ed  to  approximately  one-half  its  original  volume  and  filtered. 

On  acidifying,  the  acia  precipitated  in  needle-like  crystals  to- 
gether V(/ith  some  sodium  cjiloride.  Without  separating  from  the 
mother  liquor^  it  was  redissolved  heating  and  filtered,  thus  re- 
moving the  greater  part  of  the  salt.  On  cooling,  the  product  was 
obtained  as  colorless  crystals.  To  remove  the  last  trace  of 
sodium  chloride  an  additional  recrystallization  from  hot  water 
was  necessary.  The  yiela  of  crude  material  was  27O  g. 

In  general  appearance  and  solubility  it  resembles  the  otner 
arsonic  acids.  It  decolorizes  bromine  rapidlj^  in  aqueous  solu- 
tion, but  only  slowly  when  dissolved  in  not  glacial  acetic  acid 
or  suspended  in  carbon  tetrachloride#  An  attempt  to  convert  tne 
acid  to  the  chloroarsine  failed^ for  altnougn  an  oil  was  obtained 
on  extracting  with  etner  the  solution  saturated  with  sulpnur  di- 
oxide,, no  definite  compound  could  be  obtained  by  f ract ioiiati  on. 

Most  of  the  oil  poljnterized  to  a guKjmy  i;iass  on  heatiiig. 

Subs.  0.2  g.  : 26.4  cc.  0.09205  N I, 

Calc,  for  C3H7ASO3  : As  4^.16  0/0  Found:  As,  45.40  0/0 

it 

Benzvlarsouic  acid . 126  g.  of  benzyl  chloride  was  added  to 

the  theoretical  amount  of  sodium  arsenite  (99  g»  01  arsenious 
oxide  dissolved  in  ^00  cc.  10  N sodium  hydroxide  ).  The  solution 
was  first  heated  on  a steam  bath  and  stirred,  and  later  vigorous- 
ly boiled  for  one  hour.  The  oily  layer  was  removed  axid  tne  solu- 
tion carefully  neutralized.  A small  amount  of  flocculent  mater- 
ial which  had  separated  was  filtered  off,  and  the  filtrate  acidi- 
fied. The  acid  w'nich  precipitated  as  a vTnite  curd  v»(as  filtered 

0 

Qffj  wasned_v?ith  water ,_a.nd_dried_ at  90  iii  vacuo.  The  yielas 
* Unpublis’hed~w6rk,  “Adai/Is  “and  “JOTniTscmr  - --  --  --  --  --  -- 


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-23- 


averaged  froui  130—5  v/iiicJi  is  6O—63  0/0  of  theory  • ihe  recovered 

oil  which  was  maiiily  benzyl  alcojiol  accouiits  lor  most  ol  the  oeii— 

zyl  chloride  2iot  converted  ixito  the  arsonic  acid.  The  product 

o 

obtained  after  oxie  crystallization  melted  at  l67“S  . 

Attempt  DO  prepare  n7drox\  -ethylenearsoxiic  ac_id_. 
CHaOHCHaAsOsHa  .-On  addiiig  32  g.  of  ethylene  chlorhydrixie  to  4o  g 
of  arsenious  oxide  dissolved  in  120  cc . 10  N sodium  nydroxide  an 
immediate  reaction  took  place.  In  ten  minutes  over  70  per  cexit 
of  the  reaction  was  complete.  Since  the  acid  did  xiot  precipi- 
tate on  acidifying  the  solution  evexi  after  it  nad  been  concexi- 
trated  to  a small  volume,  it  was  evaporated  to  dryness  atid  the 
residue  extracted  with  absolute  alcohol.  After  evaporatixig  the 
alcohol  a syrupy  liquid  remained  which  presumably  was  the  desir- 
ed compound.  It  reacted  v.ith  acetic  aiihydride  although  no  defin- 
ite product  could  be  isolated.  Benzoyl  chloride  did  not  give  a 
satisfactory  result.  On  addixig  mgnesia  mixture  to  an  ammonia- 
cal  solution  of  the  crude  product,  a gelatixious  precipitate  was 
obtained  on  nefxting. 

Attempt  to  prepare  Phenoxv-etnylarsoxiic  acid. 
CeHeOCHaCHsAsOsHa  . 60  g.  of  pheno^iy-ethylbroi.aide  were  adaed  to 

a solution  of  sodium  arsenite  prepared  by  dissolviiig  60  g.  arsen- 
j ous  oxide  ixi  I80  cc.  10  N sodium  hydroxide.  Titration  of  sam- 
ples of  the  mix-cure  indicated  tnat  a slight  reaction  took  place 
during  the  first  6 hours,  and  tnexi  stopped  completely  even  tnough 
an  additional  amount  of  the  alkyl  nalide  was  added.  Even  if  a 
small  amount  of  product  may  have  been  formed,  it  was  impossible 

to  isolate  it  on  account  of  tJie  large  amount  of  arseixious  oxide 
present. 


-24- 


At  tempt  t Q prepare  Y PhenQx\^-prop\  larsoni c a.Qia  « 
CeHsOCliaCHaCHaAsOsH.  i'oliowitig  the  same  direction  outlined  for 
the  preceding  experiment,  there  was  onl}^  a very  slight  reaction 

I 

which  stopped  aoruptly.  Even  refluxing  the  solutioii  over  a. free- 
flame  did  not  produce  any  effect. 

Attempt  to  prepare  Etnvlexie  di-ArsOxiic  acid.  C2K4(  AsOsHa  )a  .- 
following  the  directi  otis  given  for  tne  preceding  experimeiit  o , no 
appreciable  reaction  was  obtained  when  ethylene  dioromide  was 
heated  and  stirred  witn  sodium  arsenite. 

Attempt  to  prepare  Irimetfn'^lene  di-Ars onic  ac ia« 

CsHc ( AsOsHs  )a  •~40  g.  of  trimeth3i^lene  dibromide  was  added  to  80  g, 
arsenious  oxide  in  240  cc.  10  a sodium  hydroxide.  I’he  mixture 
was  heated  on  a steam  ^atn  and  stirred.  At  tne  exid  of  25  nours 
70  per  cent  of  the  arsenious  acid  nad  reached  aitnougn  it  was 
necessar3^  to  add  40  g.  more  of  trimethylene  dibromide.  Six.ce 
the  product  could  not  be  precipitated  by  acia,  the  solution  was 
evaporated  to  dryness,  and  extracted  witn  alconol.  After  evapor- 
ating the  alconol  a gumuiy  mass  was  obtained  which  was  dissolved 
in  hot  water,  treated  witn  animal  criarcoal,  ana  filtered.  On 
cooling  a wnite  precipitate  separated  out  whicn  oxi  analysis  w^as 
fouiid  to  contain  over  70  per  cent  arsenic  whicn  ixiaicaoes  tnat 
instead  of  oeing  the  desired  proauct  it  was  mainly  arsexxious 


oxide 


-25“ 


2.  The  Syntiieeis  of  Areinic  Acids. 

Dibutvlars iiiic  acid.  TJiis  compound  was  prepared  by  t-vi/o  dif- 
ferent met-hods,  namely,  by  tne  Meyer  metnod,  and  by  the  condensa- 
tion of  butyl  bromide  and  arsenious  cnloride  througn  sodium.  The 
former  method,  however,  is  in  all  respects  far  superior. 

i’irst  Method. -The  preparation  of  the  secondary  acid  depended 
on  the  action  of  outvl  bromide  on  sodium  butylarsenit e wnich  was 
readily  prepared  by  dissolving  butylarsine  dicnloriae  in  an  equi- 
valent quantity  of  sodiui.i  hydroxide  soluoion.  The  exaci:  details 
of  the  experiment  are  as  follows.  6l  g.  of  butyl  bromide  were 
added  to  a solution  of  90  g.  of  but3''lars ine  dicnloride  in  l80  cc. 
of  10  N sodium  hydroxide.  Afuer  stirring  the  mixture  for  tnree 
hours  on  the  water  bath,  over  95  Per  cent  of  the  arsenious  acid 
had  reacted.  The  solution  v;as  neutralized  to  phenolphtnaieixi, 
axid  concentrated  to  about  two-tnirds  oi‘  its  origixial  vo±a-.e,  fil- 
tered, axid  tne  filtrate  carefully  acidified.  Tne  mass  of  crys tab- 
line  product  vmicn  separated  out  was  filtered  off,  wasned,  and 
u**Ted.  The  yield  of  crude  product  was  85  g.  whic/^  is  ^4  per  cent 

of  the  theory.  It  was  pure  after  one  recrystallizatioxi  from 

o 

water  as  ixidicated  oy  a coxistant  melting  poixit,  137-o  • la  pre- 
cipitatixig  tne  acid  it  is  xiecessary  to  avoid  axi  excess  sixice  this 
causes  the  product  to  chaxige  to  an  oil.  Tne  pure  compouxid  con- 
sists of  flaky  unctuous  plates  which  readily  dissolve  ixi  either 
hot  water  or  alcohol.  It  dissolves  readily  in  ammoiiium  hydroxide 
but  on  prolonged  ooilixig  the  ammoxiia  is  coiled  off  axia  tne  acids 
agaixi  separates  ixidicatixig  that  tne  ammonium  salt  is  readily  dis- 
sociated. 


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-26- 


Second  Metjiqd.  To  a well-stirred  mixture  containing  50  g. 
of  one  basic  di-n-'bu&ylarsine  chloride,  descrioea  oelow,  700  cc. 
of  water,  and  150  g.  of  ice,  a calculated  amount  (57  g*  ) 
bromine  was  added  dropwise.  A neavy  oil  colored  saightly  oy 
the  excess  of  brorniiie  collected  on  trie  oottom  of  tne  fiask.  On 
reiidering  the  solution  alkaline  witn  aimaonia  all  want  into  sol- 
ution. On  adding  magnesia  mixture  to  the  boiling  solutioxi, 
there  was  xio  appreciable  precipitation  inaicating  the  aosexice 
of  but3’’i- ar sonic  acid.  After  filtering,  the  solutioxx  was  coxi-' 
cexit rated  to  oxie-third  its  original  volume  wnereupoxx  axi  oil  sep- 
arated which  on  cooling  solidified  and  wnich  was  identified  as 
di-n-butyl-arsixiic  acid.  Repetition  of  process  brought  the 
yield  up  to  20  g.  finally,  further  coxic entrati on  yielded  an  oil 
which  showed  little  texidexicy  to  ciys ballize . 

Subs.  0.2  g : 58.8  cc.  0.105S  H I. 

Calc,  f or : CsHioAsOa  As  55»7S  0/0  Found  55*S4  0/0 
Subs.  0.5  e*  • 15‘55  02.  0.147  NaOH  Found  I5.O  cc. 

Basic  d i-bu tv lar s ixxe  chloride.  This  suostance  is  the  in- 
termediary compound  from  wnich  dibutyl  arsixiic  acid  was  prepared. 
A mixture  of  152  g.  of  arsenious  chloride  axid  200  g.  of  butyl 
bromide  were  addea  to  67  6*  of  pulverized  sodium  covered  with 
500  cc.  of  dry  oenzene  at  sucn  a rate  as  to  ixiaintaixi  a vigorous 
reaction.  In  the  course  of  three  hours  it  was  complete.  Txie 
solid  material  coxisisting  of  sodium  chj.oride  axid  a red  amorphous 
substaxice  similar  to  B'dnsen's  "Ery thrarsixi”  (51)  was  filtered 
off,  axid  the  amber  colored  filtrate  fractioxiated.  The  first 
fraction  was  almost  exitirely  benzene,  wnile  the  second  fraction 


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-27- 


0 

collected  between  100-140  consisted  of  a mixture  of  arsenious 

chloride,  butyl  bromide,  and  benzene.  ine  third  fraction  boiled 
0 

between  237—^1  • I’he  yield  was  70  g.  or  ^0  per  cent  of  t-ne 
theory,.  On  the  second  f ract i ctnation  it  boiled  at  237-S  (unc.  ), 
and  was  obtaiiied  as  a heavy  colorless  oil  containing  a smll 
amount  bY  a white  solid  which  readily  settled.  Analysis  indicates 
that  it  is  a basic  di-buty  larsine  chloride. 

Subs.  0.2940  g.  : Cl  0.0338 

Calc,  for  [[c^Eg  )3AsC^6'  [(  C4He  )aA_^aj0  : Cl  12.22  0/0  found  Cl, 

12 . 18  0/  0 

ji^em.vlarsinic  acid  ( 3^  )»-follo*iiig  ohe  directions  outlined 
for  di-n-butyl  arsinic  acid,  53  g»  ethyl  bromide  were  added  to 
90  «.  of  ethy larsine  dichloride  dissolved  in  210  cc . ol'  10  E 
sodium  hydroxide.  After  stirrixig  trie  mixture  which  was  warmed  on 
the  steam  bath  for  4 nours,  the  reaction  was  90  per  cent  complete. 
It  was  necessary  however  to  add  20  g.  more  of  ethyl  bromide  to 
replace  the  loss  due  to  volatilization.  After  boiling  off  the 
excess  of  ethyl  bfomide,  the  solution  was  neutralized  to  phenol- 
phthalein,  concentrated  to  a small  volume,  ana  filtered.  Since 
the  addition  of  acid  did  not  cause  the  separation  of  the  product, 
it  was  necessary  to  concentrate  further.  It  finally  began  to 
separate  out  as  crystalline  platelets,  together  with  a sruall 
amount  of  sodium  chloride.  The  acid  can  also  be  obtained  by  ex- 
tracting the  dry  residue  with  alcohol.  On  adaing  etner  to  onis 
solution,  the  acid  separates  in  the  form  of  iridescent  platelets. 
The  preparation  of  the  substance  entirel3^  free  from  sodium  cnlor- 


-28- 


ide  is  difficult,  and  is,  for  purposes,  uiinecessary . 

n-Propvl.  n-ButvIar sinic  acid .-This  mixed  aliphatic  second- 
ary arsinic  acid  was  readily  prepared  by  the  action  of  propyl 
bromide  on  sodium  butylarsenite . The  proportions  used  were  12. 5 
g.  of  propyl  bromide  to  20  g.  of  n-butylarsine  dichloride  dis- 
solved in  40  cc.  10  U sodium  hydroxide.  After  four  hours  neat- 
irig  and  stirring,  the  reaction  was  over  80  per  cent  complete. 

The  reaction  mixture  was  boiled  to  remove  any  excess  of  propyl 
bromide,  then  acidified,  treated  witn  bromine  water  to  oxidize 
the  unchanged  arsenious  acid  to  the  c orrespondixig  ar sonic  acid 
which  was  removed  oy  means  of  rngxiesia  mixture  after  the  solu- 
tion had  beexi  rendered  alkalixie  with  amuaonia.  Oxi  concentrating 
the  filtrate  axi  oil  separated  wnich  oxi  coolixig  solidified  to  a 
cr3rstalliiie  mass.  It  was  pure  after  one  cry stalrization  from 
hot  water.  The  acid  resembles  di-n-but3''lar sinic  acid  in  both 

physical  and  chemical  properties,  but  it  is  appreciabl3^  more  sol- 

o 

uble  in  water.  It  melts  at  127-8  4. 

Subs.  0,2  g.  0.2  g.  : 21.1,  21.0  cc . 0.09205  N I 

Calc,  for  C7H17ASO3  : As  5^.01  0/0  Pouxid:  As  5^*24  0/0 

56.12  0/0 

Attempt  tp_  prepare  n-butylphenvlar sixiic  acid. -Poll owing  the 
directions  given  for  the  preparation  of  the  other  secondaxr^-  ar- 
sinic acids,  ii-butyl  bromide  was  added  to  sodium  phexi3’‘larseiiite 
prepared  by  dissolving  phexiylar sine  di chloride  in  a calculated 
amount  of  10  14  sodium  jivaroxide.  After  heatixig  axid  stirrixig  for 
one  hour  the  reaction  was  over  90  per  cent  complete.  After  boil- 
ing off  the  excess  of  butyl  bromide,  the  free  alkali  v/as  iieutral- 


. f. 


' . -w  , . */  i.  ► * * ■ ■ I k.  i-*  . , i 


i 


. - T 


•. . ,;.  •’/ 


sJ  l - - i » U 

. , ' * . u ■ » . jL  .i-  * - •• 

.,,..-1  . ..  *J  . X . 

: i;r.'j:  . . , 1 V C'.l 

I « ■ . ',  ' J.  ■ J ''  i V.fVj 

« -V  ,t.<  i 


;i- 

}, 

i! 


K w' 


' • V. 


U > . • 1 V 


. • n.^-  i — ' 


-2  9“ 


ized,  and  the  solution  treated  v^^ith  aniiiial  charcoal  and  filter- 
ed. On  acidifying  the  filtrate  an  oil  separated  which  could  xiot 
oe  riiade  to  crystallize.  It  dissolved  coiupletely  in  aitrrionia  out 
on  prolonged  boiling,  the  oil  separated  out  agaiii.  The  presence 
of  a disagreeaole  odor  indicates  the  presence  of  an  impurity 
which  may  be  responsible  for  keeping  the  substance  an  oil. 

Attempt  to  prepare  ethvl  ohenvlarsinic  acid.  SuDstituting 
ethyl  bromide  for  n-butyl  bromide  in  the  process  described  above 
similar  results  were  obtained.  Although  the  pure  product  is 
described  as  a crj’-stalline  solid^  no  means  were  fouiid  to  crystal- 
lize the  oil  which  was  ootainea. 

f PnenvlQxv-etrivl-iJhenv  larsinic  acid.  CeH60CH2CH3(  Ceh5  ) 
AsOgH  - .-A  mixture  containing  49  g»  of  fpnei^y oxyetnylbromiue  and 
49  g.  of  phenylarsine  dichloride  dissolved  in  80  cc.  of  10  ii 
sodium  hydroxide  was  neated  on  tne  steam  bath  aiid  stirred.  At 
the  end  of  4 hours  over  70  per  cent  of  the  arsenious  acid  nad 
reacted.  After  removing  the  small  excess  of  the  unchanged  nal- 
ide,  the  excess  alkali  was  neutralized  wnereupon  the  unchanged 
phenylarsine  oxide  together  with  a small  amount  of  soapy  mater- 
ial separated.  This  was  filtered  off,  aiid  the  solution  acidi- 
fied, whereupon  an  oil  separated  vi/hich  immediately  crystallized. 

On  recrystallization  from  a large  volume  of  water  it  was  pure, 

o 

melting  at  122-9  • The  product  is  appreciably  more  solu.ble  in 
chloroform,  beiizene,  ether,  aiid  similar  solvents  thaix  tne  ordi- 
nary arsinic  acids.  A yield  of  20  g.  of  pure  product  was  obtaiii- 
ed. 


...I 

i 


.1 


r 


. J. 


r.v. 


1' . i'j  j 


I 


I 


I 


' J 


'j  ■*» 


Subs.  0.2  g.  : 14  cc . 0.09205  W I. 

Calc,  for  C14H1BASO3  : As,  24.50  0/0  ij'ound:  As  24.60  0/0, 

iiJthvleiie-diPhenYl~di-arsinic  acid . CaH4(  CeHeAsOaH  )a  .- 
52  g.  of  phexi3"larsine  dichloride  dissolved  in  120  cc.  of  10  ]ii 
sodium  h3'‘droxide  were  treax-ed  with  60  g.  01  ethj''lexie  didromide. 
After  four  hours  heatixig  50  per  cent  of  trie  phenylarsexiious  acid 
nad  reacted.  After  removing  the  ui.changed  phenyiarsine  oxide  in 
the  usual  way,  the  solutioii  was  acidified.  An  oil  wnicn  snowea 
little  tendency  to  crystallize  separated.  It  was  redissolved  in 
dilute  ammonium  hydroxide,  filtered,  and  agaixi  precipitated  by 
carefully"  acidification.  Again  the  product  came  out  as  an  oil, 
but  on  standing  solidified.  A ver3'  poor  yield  was  obtained.  Tne 
product  is  somewhat  soluble  in  hot  water  or  in  alconol.  m.  p. 
209-11. 

Subs.  0.2  g.  : 21.7  cc.  0.09205  i-'i  I 

Calc,  for  Ci4Hi.eAs204  : As  57*66  0/0  i’ound  ; As  57*55  o/d 

Subs.  0.2  g.  require sJf  8.8  cc.  1.55  1'^  I'laOH  Found:  8.4  cc. 

Attempt  to  prepare  Tr imethvlene-diphenvl-drAr s inic  ac^id. 
Triirietnylene  bromide  reacted  readily  with  sodium  phenylarsenite , 
but  on  attemptixig  to  isolate  the  product  an  oil  was  obtaixied 
which  could  xiot  be  crystallized. 


- 

i 


-31- 


3.  The  Syntheses  of  Arsenic-Sub stitu^ed  Acetic  Acids 

and  Derivatives. 

Phenvlarsonic  acid.  The  acid  was  prepared  by  the  Eart  re- 
action followiiijc:  the  German  factor3"  method  employed  during  the 
war  (24).  Since  the  method  requires  close  attention  to  details 
ill  order  to  obtain  satisfactory  results,  the  directions  follow- 
ed in  the  laboratory  are  given. 

To  prepare  the  benzene  diazonium  cnloride,  74-0  cc.  of  ani- 
line were  dissolved  in  2000  cc.  of  concentrated  ny dr ocriloric 

acid,  and  4000  cc.  of  waxer  with  enough  ice  -co  iixaintain  a tem- 

0 

perature  of  0-  10  . To  this  solution  ^60  g.  of  sodium  nitrite 
dissolved  in  800  cc.  of  water  were  graduall^^  added  with  coxistaiit 
shaking,  for  conveiiience,  the  solutions  Vi/ere  made  up  in  four 
parts  so  that  wnile  one  was  run  into  the  sodium  arseiiite  solu- 
tion, another  could  be  diazotized. 

Tne  sodium  arseiiite  solution  was  prepared  oy  mixing  toge- 
ther 960  g.  of  arsenious  oxide,  1600  g.  of  sodium  carbonate, 

450  g.  of  cupric  sulphate,  and  4000  cc.  of  water.  After  stir- 
ring this  solution  for  30  minutes,  tne  benzene  diazoxiium  chlor- 
ide was  slQwljr  added  during  the  course  of  2 f/2  to  5 hours.  To 
prevent  foaming  a little  benzene  was  frequentlj?-  added.  The  stir- 
ring- was  continued  ^0  minutes  after  all  the  solution  had  oeen 
run  in.  After  allowing  the  reaction  mixture  to  settle  over 
night,  the  clear  amoer  liquid  was  siphoned  from  the  tarry  laater- 
ial,  concentrated  until  the  separation  ol'  salt  prevented  further 
evaiyorat i on,  anu  filterea  not.  On  aciaifying  with  concentrated 
hydrochloric  acid,  the  phenyl-arsonic  acid  separated  as  a tnick 


! 


’I 


I 


V 


I 


-32- 


crystalline  mss  A^hicri  was  filtered  off  and  dried.  I'rie  yields 
were  30~33  ceiit. 

Phenylarsine  dicnjoride.  To  prepare  tnis  compound,  a slow 
stream  of  sulphur  dioxide  was  passed  through  a solution  coxitaiix- 
ing  1 part  of  phenylar sonic  and  3 parts  of  concentrated  iiydro- 
chloric  acid  to  which  a few  crj^stals  of  potassiuia  iouide  nad 
oeen  added.  The  dark  brown  oil  which  appeared  was  separated 
from  the  aqueous  layer,  and  distilled.  The  pheiiylarsine  dicnlor- 
ide  was  thus  obtained  as  a lighix,  amber  colored  oil  in  7O-85  per 
ceiit  yields  dependiiig'  upon  the  purity  of  the  ar sonic  acid  used. 

Ij^'-d r.o chloride  p-araino-phenvlarsine  dichloride « On 
passing  a stream  of  sulfur  dioxide  through  a solution  of  1 part 
of  arsanilic  acid  in  3 parts  of  eonceiitrated  hydrocnloric  acid, 
the  hydrochloride  of  p— amino— phenj^^lar sine  dichloride  separated 
as  a crystalline  mass  in  practically  quaiititative  yields. 

tanilide » Tnis  compound  was  prepared  accordiiig  to 
the  method  developed  oy  Jacobs  aiid  B^eideloerger  (33)»1.3  parts 
of  chloroacetyl  chloride  w^ere  slowly  added  to  a well  stirred  aiid 
cooled  solution  ol  i part  of  aniline  in  3 parts  of  glacial  ace- 
tic acid  and  3 parts  of  saturated  sodium  acetate  solutioii.  The 
product  separated  immediately.  A yield  of  83  per  cent  calculat- 
ed on  the  amount  of  aniline  used  was  obtaiiied. 

Cnloroacetyl  phenetidine . The  compound  m-as  prepared  iii  tne 
same  way  as  the  preceding  one  with  77  per  cent  yields. 

6 ty l~^r sani^lij:  acid . The  method  of  Jacobs  and 
Heideloerger  was  followed  (34).  A mixture  of  50  g.  of  arsanilic 
acid  and  130  g.  of  cnloroacetic  acid  were  heated  on  a boiliiig: 


-33- 


v/ater  bath  for  2 hours.  The  melt  was  poured  into  a cold  satur- 
ated solution  of  sodium  chloride,  and  the  precipitated  cnloro— 
a.cetj^'l  derivative  was  filtered , off , washed,  and  dried.  A yield 
of  55  per  cent  was  obtained . It  was  used  without  further  puri- 
f ication. 

Chloroacetvl-P-amino-benzoic  acid.  To  10  g.  of  p-amixio- 
bensoic  acid  suspended  in  a mixture  coxisistixig  of  50  cc.  of 
glacial  acetic  acid  axid  50  cc.  of  saturated  sodium  acetate  sol- 
ution, chloroacetyl  cxiloride  was  slowly  added  witn  vigorous 
stirring.  The  white  amorphous  solid  'was  i'iltered  off,  wasnea 
with  water,  and  dried.  15  g.  of  the  crude  maberial  were  ootaixi- 
ed.  It  was  used  without  further  purification,  out  a sample  for 
analysis  was  recr3^stallized  from  alcohol. 

Subs.  0.2  g.  : 0.0329  g Cl. 

Calc,  for  CsHfiOs  WCl  : Cl,  l6.62  0/0  I'ound:  Cl,  16.45  0/0 

Chloroacetvl-o-amixio-oenzoic  acid.(  35  ).  This  compound 
was  prepared  from  chloroacetyl  chloride  axid  o-amixio-oenzoic 
acid  in  the  same  wajr  as  the  precedixig  oxxe  with  similar  yields. 

Chloroacetyl -urea  (36).  Oxi  mixing  150  g.  of  chloroacetj^'l 
chloride  and  60  g.  of  urea  a vigorous  reaction  exisued.  Al’ter 
the  reaction  died  dowxi,  the  mixture  was  heated  on  the  water 
bath  for  axi  hour.  The  white  chalkj'-  solid  was  filtered  off,  wash- 
ed with  water,  and  dried.  65  g.  of  material  were  obtained. 


-34- 


Pheuvl- arsinic-(  acid  )*L.cetic  acid  and  derivatives  » 

Phenyl-arsinic~(  acid )-acetic  acid  » CeKeAsOaHCHaCOOH. -This 
compound  v/as  made  oy  the  modified  Meyer  synthesis.  121  g,  of 
sodium  chloroacetate  dissolved  in  150  cc.  of  water  was  added  to 
a solution  of  sodium  phenyl-arsenite  prepared  by  slov/ly  adding 
180  g,  of  phei:y  1-arsine  dichloride  to  a cooled  solution  of  146 
g.  of  sodium  I'lydr oxide  iii  450  cc.  of  water.  There  was  an  imme- 
diate reaction  writh  the  separation  of  a vmite  solid.  Altriough 
the  reaction  was  .90  per  cent  complete  in  30  miiiutes,  t?ie  solu- 
tion was  allowed  to  stand  several  hours.  On  adding  acid  until 
the  solution  was  neutral  to  ijhenolpnthaleiii,  the  white  solid 
w'ent  into  solution,  and  a little  tarry  material  consisting  main- 
13’'  phenyl— arsine  oxide  separated  out.  The  solutioxi  was  I’ll— 

tered,  axid  then  made  acid  to  Coxigo  red  wnereupon  the  desired 
compound  separated  as  a crj^stallixie  itass  axia  i'illea  the  coxitaiXi— 
er . A yield  of  120  g.  w'nich  is  96  per  cent  of  the  theory''  was 

o'bt.aiiied.  A portion  recrj'^stallized  from  not  vi/ater  melted  sharp- 

0 

ly  with  iitmediate  dec omposi ui 0x1  at  141—2  • Tne  compouxid  is  very 
soluble  ixi  not  water,  less  in  hot  alcohol  and  very  slightly  ixi 
most  of  the  other  conmion  solvents. 

Subs.  0.2  g.  : 17.8  cc.  0.09205  H I. 

Calc,  for  CaHe04As  : As,  30.72  0/0  Pound:  30. 6l 

Hien3".l ~chl o r 0 -ar s ixie -a c e t i c acid.  CeHBAsClCKaCOOH.-To 
prepare  this  substance,  a slow  stream  of  sulphur  dioxide  was 
passed  through  a solution  of  60  g.  of  phenyl-arsinic-acetic  acid 
dissolved  in  l3o  cc.  of  coxicentrat ed  hydrochloric  acid  to  vxhich 


-35- 


a few  cr7/stals  of  potassium  iodide  had  been  added.  The  phenyl- 

chloroarsine  acetic  acid  separated  iii  the  forra  of  plates  whicn 

were  filtered  off  and  dried.  The  yield  was  95  cent.  The 

compound  is  very  soluble  in  ether,  benzene,  or  similar  solvents, 

but  it  is  best  recry staliized  from  cnloroform.  It  melts  snarply 
0 

at  102-3  . 

Subs.  0.5  s*  • 0.0716  g.  Cl  Subs.  0.2  g.  : 15«S  cc. 

0.09205  y I 

Calc,  for  CaHeOaAsCl  : Cl  14.59  0/0  As,  d0.41  0/0 
Found  : Cl  14.52  0/0  As,  50*75  0/ • 

PhenYl-br omo-ar s ine~ac et ic  ac id . CeHsAsBrCHc COOH. -The  oromo 

compound  was  prepared  in  the  same  v;ay  as  the  precedixi^,  one.  It 

resembles  the  chloro-compo-und  ixi  chemical  and  physical  properties 

but  it  has  a lower  solubility  which  makes  purification  through 

o 

recrj’-stallizatioii  rauch  easier.  It  melts  at  115-4  . 

Subs.  0.5  g'»  • 0.1356  g.  Br. 

Calc,  for  CaHaOaAsBr  : Br  27.46  0/0  Found:  Br,  27.12. 

Attempts  to  prepare  Phenvl-Chloro-arsine-acetvl  Cnloride . 

CeHaAsClCHaCOCl . -The  preparation  of  the  acid  chloride  was  tried 

iii  several  ways.  For  the  first  attempt,  19  S*  phosphorous 

pentachloride  was  added  to  a cooleu  soxutioxi  01  20  g.  01  phenyl- 

chloro-arsixie-acetic  acid  in  75  co.  01  chloroform.  After  the 

reactioii  had  subsided,  the  solutioxi  was  heated  on  a water  oath 

for  an  nour,  then  the  solvent  axid  the  phosphorous  oxychloride 

boiled  offhand  the  residue  distilled  under  diminished  pressure. 

17  g*  of  a slightlAT^  reddish  oil  which  oii  subsequeiit  f ractiunacioxi 
0 

boiled  at  114-6  at  10  ram.  was  obtaixied.  Tne  boiling  point  ixidi- 


-56- 

cated  that  the  product  was  phenyl-arsiiie-diciiloride^  and  this 

was  subs taiit iated  by  treating  a little  of  the  oil  'with  oromiho 

wnen  crystals  of  phenvlar sonic  acid  were  obtained* 

Thionyl  chloride  was  tried  next*  On  addiiig  20  g.  of  phenyl- 

cln.oroars ine-acet ic  acid  to  50  cc  * of  thioiiyl  chloriue  coolea 

in  ice  a moderate  react io2i  set  in  which  was  complete  in  about 

0 

two  hours*  The  temperature  was  kept  oelow  20  . After  removixig 
the  excess  thioiij^l  chloride  uiider  diminished  pressure,  l6  r,*  of 
material  remained*  In  order  to  test  wnether  it  contaiiied  any  of 
the  desired  substituted  acetyl  chloride,  it  was  dissolved  i2i 
20  cc  * of  oeiizene  and  treated  witn  5 of  anirine  dissolvea 
in  20  cc  . of  the  same  solveiit.  A greexiish  crystallixie  precipi- 
tate separated  which  021  recrystallization  from  alcohol  was  oo- 
tained  in  trie  I'orm  01  long  needles  which  proved  to  oe  phenyl 
cnloroarsine  aniline  Ceh-sAsCl  AliCeKs,  (57)  for  oii  treatment  with 
water  it  decomposed  giving  phenyl-arsine  oxide  whicn  reitained 
as  a gummy  mass  and  anilixie  hydrochroride  which  went  into  solu- 
tion from  vfnich  the  aniline  was  obtained  by  the  addrtio**.  of 
ao-kali.  There  w^as  no  indication,  whatsoever,  of  the  foririation 
of  an  anilide*  Y/ith  phospnOi>.rous  trichloride  similar  results 
were  obtained* 

Attempt  to  prepare  Pnenvlarsinic  ( acid  ) a<;^Qtamide  , 
CeHeAsOaHCHa  CONE3  •-I’ollowing  the  usual  procedure,  9*5  g*  of 
chloroacetamide  was  added  to  a solution  of  22  g.  of  pheiiylarsine 

dichloride  dissolved  in  40  cc.  of  10  E sodium  hydroxide*  Altnoug! 
there  was  some  decrease  in  the  amount  of  the  arsenious  acid, 

hydrolysis  of  the  amide  went  on  much  faster  as  was  shown  oy  the 


-57“ 


copious  evolution  of  ammonia.  After  removing  the  excess  of 
phenylarsine  oxide,  t?ie  solution  was  acidified.  Ho  product, 
however,  separated  nor  could  one  be  isolated.. 

Attempt  to  pr eoare  ethyl-pheiivlarsinic  acetate . 
CeK5As02HCH3C00C3B'.5 . -Ethyl  chloroacetat  e was  allowed  to  react 
with  sodium  phenylarsenite  made  in  the  usual  manner.  A vigor- 
ous reaction  ensued  followed  by  the  separation  of  a gummy 
mass  which  consisted  partly  of  pherylarsine  oxide  and  presuni- 
ahiy  partly  of  the  desired  product.  It  wa.s  found  difficult  to 
isolate  the  product  so  the  work  was  abandoned. 

Pheuvlarsinic  (soicO  acetanilide. 

CeKeAsOaHCEs CONHCeHf? .-  The  Meyer  reaction  was  employed  for 
the  synthesis  for  this  compound.  53  g.  of  phenylarsine  di- 
chloride were  dissolved  in  63  cc.  of  10  H. sodium  hydroxide 
(a  3 per  cent  excess  over  that  required  by  theory).  To  tnis 
solution  27  g.  of  chloroacetaniride  Mere  added  with  stirring 
to  obtain  a homogeneous  mixture.  As  the  reaction  proceeded, 
a consiaerable  amount  of  heat  was  evolved,  and  the  chloro- 
acetanilide  disappeared.  After  three  hours  the  reaction 
was  complete.  The  solution  w^as  then  diluted  witn.  axi  equal 
voluiae  of  water,  and  enough  hydr oc/iloric  acid  added  to 
make  it  neutral  to  phenolphthalein  when  the  unchanged  pheny- 
larsine oxide  precipitated  as  a gumray  mss.  This,  together 
with  small  traces  of  unchanged  chloroacetanilide , was  filter- 
ed off,  and  the  clear  filtrate  acidified  until  acid  to  Congo 
red,  whereupon  the  desired  product  was  completely  precipi- 


-58- 


itated.  It  was  filtered  off,  washed  witJi  a large  volume  of  not 
water,  and  dried.  50  of  material  were  obtained  which  corres- 
ponds to  a 90  per  cent  yield.  It  can  toe  furtne  r purified  b3!^  re- 
crystallization from  hot  water  in  which  it  is  very  sparixigly 
soluble.  A sample  tnus  prepared  consistea  of  tiny  clusters  of 
needle  crystals  melting  at  lS2-5^  witii  evolution  of  gas.  Tne 
compound  is  insoluble  in  oerizene,  chloroform,  caroon  tetracnlor- 
ide,  acetone,  ether,  or  similar  solvents,  tout  it  is  appreciaoly 
soluble  in  glacial  acetic  acia  ana  somewnat  ixi  etnyl  and  metnyl 
alcohols.  It  is  a fairly  stroiig  acid  liberating  cartooxi  dioxide 
from  carbonates. 

Subs.  0.2  g.  : 12.2  cc.  O.IO59  K I 

Calc,  for  Cl 4H14 OsHAs  : As,  23»50  0/0  Jound:  As,  25«75‘ 

Phenvl-bromoarsine-acetanilide.  CeHoAsBrCHa CONKCelie  .-A  slow 
stream  of  sulphur  dioxide  was  passed  through  a cooled  solution 
of  20  g.  of  phenylarsinic-acet ic  acid  in  a mixture  of  10  cc.  of 
glacial  acetic  acid,  20  cc.  of  concentrated  h3''drooromic  acid, 
and  50  cc.  of  water  in  which  a few  crystals  of  potassium  iodide 
?’ad  been  dissolved.  An  oil,  which  in  the  course  of  the  reaction 
hardened  to  a semi-solid  substance  together  with  a mass  of 
crystals  separated.  The  3''ield  of  dr3r  product  was  17  g.  On  re- 
crystallization from  methyl  alcohol  a wnite  crys&alline  product 
melting  at  loS-110  was  obtained. 

Subs.  0.2  g,  : 11.7  cc.  0.09205  H I.  Sues.  0.4  g.  : 

0 . 0894  g Br . 

Calc,  for  Ci4Hi3As0i\IBr  : As,  20.47  0/0  Br,  21.85  0/0 

Bound:  As,  2O.15  0/0  Br,  22.56  0/0. 


->9- 


Pheiiylarsinic-acetyl-phenetidine . CeHsAsOsHCHaCONHCeHsOCahe  •V'J 

This  compound  v\?as  prepared  in  the  same  way  as  the  correspoiiding 

aniline  derivative  encu^i-  i.hat  an  equal  volume  of  alcohol  was 

added  to  the  reaction  mixture.  l8  g.  of  the  chloro-acetj'^l-phene- 

tidine  was  added  to  19  g-  of  phenylarsine  dichloride  dissolved 

in  59  cc.  of  10  N sodium  hydroxide.  Only  9 g*  of  product  were 

obtained,  but  subsequent  work  shows  that  much  better  yields 

could  be  obtained  by  the  omissioxi  of  the  alcohol.  The  compcuiid 

is  appreciably  more  soluble  in  hot  water  and  alcohol  than  the 

corresponding  anilide.  It  is  best  recrystallized  from  alcoriol 

from  which  it  can  be  ootaiiied  as  needle  crj^stals  whicri  melt  at 
0 

175  with  decomposition. 

Suos.  0.2,  0.2  : 10. 7 > 10.75  oc.  0.1058  iJ  I. 

Calc,  for  Ci4Hi804kAs  : As,  20.65  0/0  Pound : as,  20. Si  0/0 

20.91  0/0 


PhenYlarsinic--acetYl-arsanii.ic  acid . 
CeHsAsOaKCHaCOllHCeHeAsOsHs  (p).  51  S*  of  the  sodium  salt  of 

c'hloroacetyl-arsanilic  acid  dissolved  in  50  cc.  of  water  was 
added  to  the  theoretical  amouiit  of  sodium  phenyl-ars enite  (22  g. 
of  phenyl  arsine  dichloride  and  50  cc.  8 iJ  sodium  hydroxide). 

The  reaction  was  complete  in  2 hours.  After  the  addition  of 
acid  until  the  solution  was  neutral  to  phenolphtnalein,  the  un- 
changed phenyl-o.rsine  oxide  was  filtered  off,  and  the  product 
precipitated  by  acidification.  Trie  chalky  precipitate  was  fil- 
tered off,  extracted  first  with  a large  aiaount  of  hot  water,  then 

o 

with  hot  alcohol,  and  finally  afied  at  110  . It  is  insoluble  in 


r!,  , 

• , ♦ * 

>>  J . L - * w 

Eg 

111 

. ■ . . .' 

i,jOS 


U 


/ 


**  r-  ‘ • ** 


i,  . . . 

‘ \ ^ ' it  • ^ 

-I  I : : 

• r . f ^ 

».  * V •-■-'  ; ^ 

*.c 


.•ti 


i'C 


*v.  r \ 


-40- 


all  thp  common  solvents,  wjiich  prevents  its  purification  through 
recr3’ stallization.  It  can  however  be  converted  into  its  soluble 
sodium  salt  aiid  reprecipitated  by  acidification.  Ine  product 
even  without  recrystallization  is  pure  as  indicated  by  tne  ana- 
lysis. The  yield  was  around  70  per  ceiit. 

Subs.  0.2,  0.2  : 17.4,  17.4  cc.  O.IO^^S  a 
Calc,  for  Ci4Hi60el>iAs3  : As,  3^.84  o/o  found:  As,  33.84  o/o 

33»h4  o/o 

Pnenvlarsinic-acetyl-o-axiiino-benzoic . 
CeH6As02HCH3C0NHCeH5C00K  (h)  The  saj:ae  procedure  as  for  preceding 
preparation  was  used.  22.5  g.  of  sodium  cnloroacetyl-o-a.-ino- 
benzoate  in  50  cc.  of  water  was  added  to  the  calculated  amount 
of  sodium  pheiii^l-arsenite  solution  (22  g.  of  phanylarsine  di- 
chloride in  40  cc.  of  10  N sodium  ?iy droxide  ) . The  precipitation 
was  conducted  as  before.  Since  tne  product  was  too  insoluble 
to  be  purified  by  recrystallization,  it  was  dissolved  in  dilute 
sodium  carbonate  solutioii,  boiled  with  animal  charcoal,  filtered, 

aiid  reprecipitated  by  means  of  hydrochloric  acid.  It  is  a white 

0 

chalk^v  powder  which  melts  with  decomposition  at  198-200  C. 

Subs.  0.2  g.  : 11.9  cc.  0.09205  W I 

Calc,  for  Ci5Hi40Bh’As  : As  20.65  0/0  found:  As,  20.47  0/0 


-41- 


Derivat ives  of  P amino  ohenvl  arsinic  (acid)  acetic  acid . 

P-Aiiiino-nhenvlars  Inic-acetanilide  « ( p )H3NCeH4AsO2HCKaCOKHC0iij^ 

This  compound  was  prepared  oy  adding  34  g of  chloroaceianilide  to 
a solution  of  sodium  p-amino-phenylarseni^e  prepared  by  dissolv” 
iiig  38- g of  the  hydrochloride  of  p-amino-phenylars ine  dichloride 
iii  100  cc.  of  10  li  sodium  hydroxide.  A reaction  set  in  iinmediate- 
ly  and  was  complete  in  one  hour.  After  standing  for  several  hours 
the  solutioiiwas  rendered  neutral  to  phenolphthalein,  the  small 
amount  of  unchang'ed  p-amino-phenylarsine  oxide  together  with 
traces  of  unchanged  chlor oacetanilide  filtered  off,  and  tne  solu- 
tion treated  with  concentrated  hydrochloric  acid  until  just  acia 
to  Congo  red.  Excess  aciaity  v;ae  avoided  to  prevent  part  of  the 
product  beixig  redissolved  on  account  of  trie  presexice  of  the  amino 
group.  A 3^ield  of  42  g,  which  is  64  per  cexit  of  theory  was  oo- 
tained.  It  could  readily  be  purified  eitrier  from  alcohol  or  hot 
water.  It  is  oxilj^  slightl3^  soluble  in  methyl  alcohol,  axid  acetoxi.e 
axid  iiisoluble  in  benzexie,  ethyl  acetate,  etner^  or  similar  sol- 
vents. The  pure  product  melts  at  l8l-2^  w/ith  evolution  of  gas. 
Subs.  0.2  : 13  cc.  0.09203  N I 

Calc,  for  Ci-iEisOaNaAs  : As, 22 .44  Fouxid  : As,  22.36. 

E-Ace  tv  l-P-aiaino-Ohenvlarsixiic-acetaxiixide . 
CHsCONKCeRsAsOsHCHsCOHHCeHE  .-This  acet3'  l derivative  wasrreadily 
prepared  by  warming  a mixture  of  10  g.  of  the  axiilide  axid  13  cc. 
of  acetic  anhydride.  As  soon  as  the  reactioxi  started,  the  flask 
was  wrapped  ixi  a tov<iex  to  coxiserve  the  heat  of  reaction.  When 
the  main  reaction  was  over,  the  mixture  was  heated  on  one  water 


V 


■'1 


k 


...  L.  J,  -J.'.., 


. if',  C'-'  i ■■  , .•ii'l- 


w 

..,(>  a»>' 


, > 

• ’.  ' 


‘•V.  t\ 


f - »K  V / * > J.  X , ■*'  1,  .0  V * %j  ^ .1. ji  ■ ■•-  -J 


, , • i i A.  i-  • ' 

V 


H 


i 


} 


(Jil  ..t ; 


- t'  -.  \ i . 


1 L.* 


f I 


-42“ 


bath  for  15  iniiiuteG,  then  diluted  with  five  parts  of  water 
whereupon  tne  desired  substance  prec ipitatea . It  was  I’iltered 
off,  extracted  with  dilute  hydrochloric  acid  to  remove  aiiy  of 
the  free  amino  compound,  thoroughly  washed  with  v^ater,  ana 
dried.  Almost  quantitative  yields  were  obtained.  It  was  recrys- 
tallized from  hot  water.  It  consists  of  elongated  platelets 

0 

which  melt  at  205-6  with  decomposition. 

Subs.  0.2  g,  0.2  g.  : 11.65,  11«65  cc.  O.O9205  cc . N I 
Calc,  for  CieHi704N3As  : As,  19»94  0/0  ]?ound:  As,  20.04  0/0 

20.04  0/0 

H-g  Ivcvl-D-aruino-DhenYlars  ini  c -acetanilide . 
HOOCCHsNHCeK^AsOaHCHaCONHCeHB .-The  glycyl  derivative  was  prepar- 
ed from  p-amino-phenyl-arsinic  acetanilide  by  heating  10  g.  of 
it  dissolved  iii  50  cc.  of  4 per  cent  sodium  h3^droxide  solution 
containing  7 of  chloroacetic  acid.  After  refluxing  for  ^^4 
hours  the  solution  cleared  with  the  separation  of  a small  amount 
of  oil.  The  refluxing  was  continued  about  4 hours  during  which 
period  a granular  solid  separated  out.  In  some  ruixs  the  Ablu- 
tion reKiained  clear  until  cooled  when  an  oil  separated  which  on 
standing  turned  crystalline.  The  product  could  be  recrystalliz- 
ed from  methyl  alcohol,  but  simple  extract! Oii  with  hot  water  or 
a small  amount  of  hot  alcohol  seemed  to  remove  all  impurities 
leaving  a white  product  meltirig  at  199^^  with  decomposition.  The 
yield  of  crude  product  was  6 g. 

Subs.  0.2  g.  0.2  g.  : 11.15,  11«2  cc.  0.09205  li  1 

Calc,  for  CieHiaOBHaAs  : As,  19*12  0/0  Found:  As,  19*lS  0/0 


19.26  0/0 


t - 


> 


jL 


lx.  i. 


I . 


A 


> 


-43- 


p-Ajiiino  phenvlarsinic-acetvl-o'rienetidine » 
HsNCeKfAsOaKCHsCONHCeH^OCsHsCp  ) 21  g.  of  chloro-acetyl  phene- 

tidine  were  added  to  t?ie  calculated  aiaount  of  sodium  p-amino- 
phenylarsenite  (29  g*  of  the  hydrochloride  of  p-amino- phenyl 
arsine  dichloride  in  ^0  cc.  of  10  if.  sodium  hydroxide).  The  re- 
action was  complete  in  three  hours.  After  precipitat iiig-  the  un- 
changed p-amino-phenylarsine  oxide  by  reiidering  the  solution 
neuiiral  to  phenolpntnalein,  and  filtering,  i-he  product  was  ob- 
tained by  further  additioii  of  acid.  li  is  suff iciexit-lj^  soluble 
for  recrystallization  from  either  hot  wafer  or  alcohol,  but  is 
best  purified  by  means  of  the  latter  solvent.  In  its  chemical 

and  physical  properties,  especiallj^  soluoility,  it  resembles 

0 

the  correspondizig  anilide,  d*  p.  201. 5-202. 9 . 

Subs.  0.2,  0.2  : 11,5  cc.  11.5  cc.  0.09205  N I 

Calc,  for  CieHi0O4N3As  : As,  19*83  0/0  PoundlAs,  19*78  0/0 

19*78  0/0 

K Acetyl-p-amino-phenvlarsinic-acety  1-phenet idine . 
CHsCONHCeHfS^AsOaHCHaCONHCeK^OCaHsC  p )*-The  acetyl  derivafive  was 
prepared  in  the  same  manner  as  the  corresponding  aniline  deriva- 
tive already  described,  from  10  g.  of  the  free  amino -compouxid 
-created  with  I5  cc  . of  acetic  anhydride,  12  g.  of  unpurified 

product  were  obtaixied.  After  recrystallization  from  alcohol,  a 

0 

crystalline  soo.id,  melting  at  214-5  with  tne  evolution  of  gas 
was  obtaixied. 

Suds.  0.2,  0.2  g.  : 10. 3,  10. 3 cc.  O.O9205  i'j  I 

Calc.  CisEsiOeiiaAs  J As,  17.84  0/0  found:  As,  17*>72  0/0 

17.72  0/0 


V-i 


I 


I 


' \ 


, . i. 


J 


'zrr 


*/■ 


I 


T“P“< 


-44- 


i.-C7lvcvl-P-aa;iijiQ-T)heiivlarsinic-acetvl-phenet_idj4M» 
HOOCCHartHCeHifAsOaHCHaCOIIHCeH^OCaHe  (p).  Although  the  same  methoc 
which  was  used  for  the  correspoiiding  aniline  compound  was  fol- 
lowed the  j^ields  were  very  poor.  10  g.  of  the  amino  compound 
were  dissolved  in  20  cc . of  4 per  cent  sodium  hydroxide  solution 
and  refluxed  with  6 g.  of  chloroacetic  acid  f or  8 hours.  Only 
3 g.  of  product  was  obtained.  It  was  exceedingly  difficult  to 
purify  the  crude  material,  the  purest  product  being  obtained 
by  merely  extracting  the  material  with  boiliiig  water  which  re- 
moved the  more  soluble  impurities.  A sample  thus  prepared  melt- 
ed at  197^  with  ii^imediate  decomposition. 

Suds.  0.2,  0.2  : 10.1,  10.1  cc.  0.09203  h I 

Calc,  ior  Ci sHaaOePaAs  : As,  17»19  o/o  xO.iiid:  As,  x9»37o/o 

19.370/0 

Q-Ataino-phenvlarsinic-acetYl-arsanilic  acid. 
Hai.CeHfAsOiiHCHaCOj'jIiCeHf  AsOsHa  •-I’he  comp ouiid  was  prepared  by  add- 
ing 29  g.  of  chloro-acetyl-arsanilic  acid  dissolved  in  40  cc.  3 
N.  sodium  hydroxide  to  the  theoretical  amount  of  sodium  p-aiiiino- 
phenyl  arsenite  prepared  by  dissolving  29  g.  of  che  hydrochloride 
of  p-amino-phenyl-arsine  dichloride  in  30  00 » 10  N soaium  1 

hydroxide.  A considerable  amount  of  heat  was.  evolved  in  the 
reaction.  After  three  hours  the  solution  was  rendered  iKsutral 
to  phenolphtnalein,  boiled  with  animal  charcoal,  and  filtered. 

The  filtrate  wa.s  carefull3^  acidified,  avoiding  an  excess  of  min- 
eral acid  which  would  redissolve  the  product^  and  the  white 
chalky  solid  which  separated  was  filtered  off,  extracted  with 
hot  wax,ei , and  dried.  The  product  was  f ou2id  suff icioiitly  pure 


1-ts' 

\ ; ■ 7^%i 


i ' ‘ '“" ' ''  ■'  ■ *"* 

I , w . •..  ^ ...  . ,1  i • I-  , '*  ” ' / 'Vj'J  , 


^ - , .... 

{j  I-  w, 

O'J  J»f  ' 

J.  . '* 

.i;.: 

4 • • ' . '•?  ' • ‘ ■ 

yj.  X ';; 

- 

( 

r : V.  t.;  . "■ 

L L-v*’v  .1 ..X 

!?  •••  • ^ • 

. \ . ..  ... 

t ..  v;  ^ . 

. r 

L*: ' 

ii 

..  J i.  1-  • 

, L . . : ’1  . V 

T . . S “*■•  • 

O : . >-■  ■ 

* 

ii  . 

; k i • . • V ••  C-  • ' >•'  *■ 

^ / ' V i ^ ^ V.  ^ ^ 

i .44^ 

is 

_ - r 'f 

i j, 

. ..  ■'.:L.  i-'J-i  J .- s. 

..  v..^. 

\\, 

S; 

i* 

...‘  - 1 j 



• » * • .4-  *.  Jw  ^ » 4 4 '■  • V4.  - » ^ ‘ 

i' 

• j.  ‘ - 

, 

( 

..,  CO.v^‘ 

’ 4 * ^ ' « • • 

•>*  V.. 

: :,:yi.  : 1. .-.■■■>  v - • , ..t. 

I 

, J.  ■ , . ••v~V'  ■;  ^ * '•  ' 


-45- 


for  the  purpose  at  hand,  but  a sample  for  analj^sis  was  recrys- 
tallized from  hot  water  in  wnich  it  is  very  sparingly  soluble. 

A yield  of  25  g,  or  53  cent  was  obtained.  In  some  runs  a 

0 

product  which  turned  yellow  especially  when  dried  at  aoout  100 

was  obtained.  This  trouble  was  avoided  however  oy  coiling  the 

reaction  mixture  with  aiximaj.  charcoal  cefore  precipitating  cn.e 

acid,  and  by  extracting  the  product  thoroughly  with  hot  water. 

0 

The  compound  does  not  melt  but  turns  dark  at  25O-6O  . 

Subs.  0.2,  0.2  : 18. S,  18.9  oc.  0.02205  H I- 
Calc,  for  Ci4Hie0eN2As3  : As,  32«73  0/0  l?ou**a:  As, 

32.51  0/0 

N-Acetyl-o-amino-ohenylarsinic-acetyl-arsanilic  acid. 
CHsCONHCeHi^AsOaHCHaCOi'raCeHifAsOsHa*^.''-  10  g.  of  the  free  amino 
compound  were  treated  with  15  cc.  of  acetic  anhydride  and  heated 
until  the  reaction  set  in.  The  product  was  throwii  out  of  solu- 
tion by  diluting  the  solution  with  4 parts  of  water.  The  yield 
was  poor.  Hie  sample  for  analysis  was  prepared  by  recrystalli- 
zation from  hot  v^rater. 

Sues.  0.2,  0.2  g.  : 17.3,  17*35  *20*  0.09205  h I. 

Calc,  for  Cl 6H18O7N3AS2  : As,  29. 9S  0/0  i'ound:  As,  29*75  o/< 

29*S9  0/0 

p -/umihO-pnenylar s inic -ac e tv  1-P-atii.ino  beiizoic  acid . 
H24CeH^As03llCH.2 C0EHCeHi$«c00H  (p).-The  usual  procedure  was  follow- 
ed for  the  preparation  of  tnis  cojnpound.  42  g.  oi’  chloroacetyl- 
p-amino-benzoic  acid  dissolved  in  10  cc.  10  W sodiuxt  hydroxide 
was  added  to  the  calculated  aiaount  of  sodium  p-amino-pheny lar- 
senite  (58  g.  of  the  hydrochlorid e of  p-amino  phenyl  arsine  di- 


I 


< 


f 


I 


! . 


I 

I 


l< 

k' 

f 


t 


« 


• j 


ir- 


f. 


I 


I 


. J 


r*; 


•44 


-46- 


chj.oride  in  100  cc.  10  N sodium  ii^'-droxide  ).  A ^0  per  ceiio  yield 
was  obtained.  To  purify  the  product  it  was  found  oest  to  re- 
crystallize from  a small  volume  of  hot  water  usiniu  the  filtrate 
again  as  solvent  since  an  appreciable  amount  of  suDstaiice  reiaains 

in  solution.  The  purified  compound  consists  of  needle  crystals 
0 

melting  at  217  with  decomposition. 

Subs.  0.2  g,  : 11.4  cc.  0.09205  N I 

Calc,  for  Cl  4H1  sOfsKaAs : As,  19*83  0/0  Pound:  As,  19*60  c/o 
p-Aniino-'Phenvl  arsinic-acetvl  urea  .HallCeH^AsOaKCHa  COilHCOiiHa  • 
Xue  Caiciuiri  salt . On  mixing  8 g.  of  chlor oacetyl-urea  wit'h  a 
solution  of  15  g.  of  the  hydrochloride  of  p-amino-phei]5"larsi.*e 
dichloride  in  25  cc . 10  h sodium  hydroxide,  the  arsenious  io^ 
disappeared  to  the  extent  of  90  per  cent  in  1 hour.  After  remov- 
ing the  excess  of  phenylarsine  oxide  in  the  usual  manner,  the 
solution  was  rendered  alkaline  with  a.mmonia  and  treated  vi^ith  a 
solution  of  calcium  chloride  w'nereupon  a sandy-like  substance 

separated  out.  It  was  amlyzed  without  further  purification. 

0 

Subs.  0.5  g.  : 0.0726  g.  HaO  loss(  heating;'  at  110  for  1 hour 
Subs.  0.2  g.  : 12  cc.  0.09205  b I 


Care,  for  CisHsaAsOsNe  Ca  . 6H2O  : H3O,  14.52  0/0  As,  20.05oyO 
Pound:  H3O,  14.44  0/0  As,  20.64  0/0 


1 


rl 


|1 


K' 

<■ 


(I 


-47- 


SUidiuAHY 

The  keyer  Reactioxi  was  modified  by  substituting  eitner  an 
alhyl  bromide  or  chloride  for  a««  alhyi  iodide,  by  omitting  alco- 
nol  as  a solvent,  and  by  heating  and  stirriiig  the  reaction  mix- 
ture . 

Methyl,  ethyl,  n-propyl,  n-butyl,  and  allyl  ar sonic  acids, 
the  last  two  of  which  are  new,  were  prepared  by  tne  modified 
Meyer  reaction.  The  method  failed  for  the  preparation  of  iso- 
pro  pylarsonic  acid, ethylene  di-arsonic  acid,  tri-methylene-di- 
arsonic  acid,  f phenoxy-ethy^lar sonic  acid,  and  y pnenoxypropyl- 
arsonic  acid . 

n-Butyl  and  ethylarsine  dichloride  v/ere  prepared  by  reduc- 
ing the  correspondiir’’  arsoiiic  acids  dissolved  in  concentrated 
.hydrochloric  acid  with  sulfur  dioxide. 

A number  of  dialhylarsinic  acids,  includiiig  dietnylarsinic 
acid  di-n-but3^1arsinic  acid,  and  n-outyl-i.-propylarsinic  acid  of 
wnich  fhe  last  two  are  new,  were  readily  prepared  by  the  li.odifi- 
ed  method.  A few  special  types  of  compounds  such  as  f phenos^- 
ethyl-pheiiylarsinic  acid  were  also  made. 

An  attempt  to  prepare  aromatic -aliphatic  arsinic  acids  fail 
ed  since  the  product  which  was  obtained  as  an  oil  could  *.ot  ^e 
crystallized. 

Phenylarsi2iic-acet ic  aciu  was  prepared  by  the  actioxi  of 
cnloroacetic  acid  on  sodium  phenylarsenitw-.  It  was  reduced  to 
pnei.yl-chloroarsine-aceti c acid  bj^  means  of  sulfur  dioxide.  On 
attempt  to  convert  the  latter  compound  to  the  acetyl  cnloride 


^ rm 


i 


>J 


1.  ii.l.  *‘  ■ 


•V 


L 


y- \ 


,.v‘ 

vl...  , 


. ii  J 


W Ai- 


i. 


^1 


I 


- f . / . , , . ;...•,*.  4. . 


.;. 


i.  ‘ . i 


’ >'  * 


.1 


, V 


' ‘ y. 


♦ 

I 


I 


I 


I 


-48- 


derivative  failed  since  the  necessary  reagents  split  the  arsine 
radical  from  the  acetic  acid  group. 

A number  oi'  aromatic  substituted  amides  of  phenylarsinic- 
acetic  acid  were  prepared  by  the  actioii  of  the  correspondiiig 
chloroacetyl  derivative  on  sodium  phenyl-arsenit e«  A similar 
series  of  derivatives  of  p-amino-phenylarsinic-acetic  acid  were 


also  prepared 


4TVjh)L^i|MBK 

'-  I*  ^ ’ T 

' . • I V "i 

itr.  n!i 


•\  ■'  ■"  'V-W'Prs 
^ V \.  ..  i 


-A  % 


>■ 


b ' " ; j'  ’••’*>•'  „ -.,;>•  • , ■.'>>■ 

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LSI*  -A^>i 


PART  TI 

The  Action  between  Secoiidary  Arsines  and  Alde’riydes* 


-49- 


THEORETICAL 

Recently  Adams  and  Palmer  (58)  found  that  primary  arsines 
reacted  with  aldehydes  to  ;^ive  an  addition  produce  to  v/hich 
they  assigned  the  structure:  ( RCHOH )3As.R.  In  order  to  find 
v;hether  this  reaction  can  oe  extended  to  the  secondary  arsines, 
this  work  was  undertaken. 

Dipneny''larsine  was  chosen  as  a representative  secondary 
arsine,  while  benzaldehyde  and  butyr-aldehyde  as  aromatic  and 
aliphatic  aldeh3^des  respectively.  The  arsine  reacted  with 
both  aldehydes,  but  in  Doth  cases  tne  additioii  product  was  too 
unstaole  and  too  sensitive  to  oxidation  to  permit  its  isoiatiox*. 
The  reaction  v;as  not  an  oxidation  of  the  arsine  by  the  alde- 
hyde, for  in  the  first  place,  no  reduction  products  of  the 
aldehyde  could  be  detected,  aiia,  ix*  the  secoiid  place  tne  reac- 
tion mixture  before  beii]^:  exposed  t 0 air  uissoived  completely 
in  ether,  whereas,  the  oxidatioii  products  of  diphenylarsine, 
especially  diphery’-larsinic  acid,  are  out  siightly  soluble  in 
t'hat  solvent.  It  was  further  found  that  a luucn  larger  part  of 
the  arsine  aiid  alde'h3'’de  than  could  be  accounted  for  as  unchang- 
ed material,  Judging  from  the  intensity  of  the  reaction,  could 
be  recovered  by  fractional  distillation  under  diminisned  pres- 
sure . 

The  experimental  evidence,  especiall3^  in  the  case  of  ben- 
zaideh3'-de,  pointed  to  the  formation  of  an  additioii  product  which 
vvhen  exposed  to  air  immediately  underwent  oxidation  wicn  suose- 
quent  cleavage  giving  benzaldehyde  again  and  the  oxidation  pro- 
ducts of  phenylarsine . The  y§P^F.f^ipn  of  a solid  to  the  extent 


-50 


that  the  vmole  solution  solidified  indicated  tnat  a large 
amount  of  a solid  product  was  formed.  This  was  not  aipheiiyi- 
arsinic  aoia  or  pheiiiylcacod:^' 1 since  ootn  are  spariiigly  soluble 
in  ether,  wnereas  the  reaction  mixture  dissolvea  corapietely 
in  that  solveiit.  li’urthermore,  it  seemed  improbable  tnat  it 
was  mainly  phenyl-arsine  oxide  since  this  suostance  was  never 
found  present  in  large  amount. 


A possible  explanatioii  of  rhe  reaction  is  as  follows:- 

(CeH5)2AsH  + RCHO  —>  ( CeHe  ^aAs  - CHOHR 

■■  ii 

( CeHe  )2AsCH0HK  — > ( Ceils  )2As  ^ — R~:^(  CeHs  }3As  + KCiiO 

0/  rf  0 


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-^1- 

EXPKRIMENTAL 

Diphenylarsinic  acid « This  substance  was  prepared  from 
diphenylarsine  chloride  obtained  from  the  Chemical  Warfare  Ser- 
vice. Instead  of  preparing  the  acid  directly  by  passiiig  chlor- 
ine through  an  aqueous  suspension  of  diprienylarsine  chloride(  39  ) 
a slow  stream  of  chlorine  was  passed  through  a solution  of  di- 
phenyl-arsine chloride  in  dry  benzene.  Dipheiiylarsiiiic  chloride 
immediately  began  to  separate  out.  The  white  cri’stalline  pro- 
duct was  filtered  off,  aiid  the  adheriiig  benzene  allowed  to  evap- 
orate. To  obtain  the  acid,  the  chloride  was  covered  with  a 
large  volume  of  water  when  it  avdrolyzed  to  the  acid.  The  pro- 
duct is  insoluble  in  water  and  can  be  filtered  off  and  washed 
free  from  impurities.  Quantitative  yields  were  obtained. 

Diphenvlars ine . The  arsine  was  obtained  according  to  the 
directions  of  Dehn  and  V/ilson  (16)  by  the  reduction  of  diphenyl 
arsinic  acid  " v/i  ui  amalganiated  zinc  dust  and  coiicentrated 
hydrochloric  acid.  Generally  ^0  g.  of  the  acid  v^rere  mixed  with 
100  g.  of  zinc  dust  aiid  covered  with  200  cc.  of  ether.  About 
250  cc  . of  concentrated  hydrochloric  acid  were  added  dropwise 
in  the  course  of  three  days  with  intermittent  stirring.  This  ■ 
reaction  was  carried  out  in  a 2 liter  flask  provided  with  a me- 
c’nanical  stirrer,  a long  reflux  condenser,  axid  a dropping  funnel. 
On  the  completion  of  the  reaction  the  bluish  colored  ether  layer 
was  siphoned  off,  dried  over  fused  calcium  chloride,  and  then 
fractionated.  The  arsine  was  obtained  as  a colorless  highly 
refractive  liquid  boiling  at  173-177  at  3I  .nn.  in  6O-70  per  cent 


LIBRARY 

UNIVERSITY  OF  ILLINOIS 


-52- 


yields. 

Coiidensat ioti  with  Benaaldehyde . To  5^  S*  arsine  kept 

in  a srmll  flask  in  an  atmosphere  of  carton  dioxide,  15  of 

tenzaldehyde  and  a few  drops  of  hydrochloric  acid  v/ere  added. 

The  mixture  imciediately  begazi  to  heat  up  and  in  a few  rniiiutes 

solidified.  On  warmijog  slov/ly  in  a water  oath,  tne  mass  melted 
0 

at  about  60  with  preliminary^,  softening,  and  on  cooling  resoli- 
dified. When  subjected  to  vacuum  dis filiation,  a large  part  of 
the  benzaldehyde  was  recovered,  but  trie  liquid  remaining’  cuuld 
not  be  distilled  without  decomposition.  The  mixture  dissolved 
almost  completely  in  ether.  As  soon  as  the  solid  was  exposed  to 
the  air,  it  heated  up,  became  plasted,  then  oily,  and  eiuitted  a 
strong  odor  of  benzaldehyde . On  extracting  -cne  product  with 
sodium  carbonate  after  it  h£id  been  exposed  to  the  air  most  of 
it  went  into  solution,  ana  on  acidify^-ing  yielded  diphenvlar sinic 
acid  vlhich  was  identified  oy  a mixed  melting  point.  The  residue 

on  recry’’stallization  from  benzene  yielded  crystalline  diphenyl- 

0 

arsine  oxide  melting  at  89-90  . No  other  products  seemed  to  be 
present . 

Condensation  with  Butvr-ald ehvde . On  treating  53  g»"ams  of 
diphenyl  arsine  with  10. 5 g.  n-butylaldehy de  and  a few  drops  of 
concentrated  hydrochloric  acid,  a vigorous  reaction  ensued,  with 
the  liberatioxi  of  a considerable  amount  of  heat.  On  cooling  the 
product  solidified.  Ey>^  fractional  distillation  under  diminished 
pressure,  9 g»  of  the  aldehy^de  ana  25  grams  01  the  arsine  were 
recovered.  A siuall  amount  of  a heavy  red  oil  remained  wnicn 
could  xiot  be  distilled  without  decomposition.  By  extracring  tnis 


oil  witn  Eodi'i^rii  carboziate,  and  subseciuenu  acidif icax-ioxi  ol  i/he 
extract,  a considerable  amount  of  dipheuylarsinic  acid  was  oo— 
taiiied  showing  that  this  substance  was  the  maiii  constituexit  of 
the  oil.  No  condensation  products  could  be  isolated. 


-54- 

SUMkARY 

The  reaction  oe tween  diphenylarsixie  axid  two  axdenyuee, 
GUtyl  and  Derisaldehyde,  was  stuaied.  In  ooth  cases  a reaction 
took  place,  presumably  wizh  the  formation  of  an  addition  pro- 
duct, v/hich  was  too  unstable  and  too  sensitive  to  oxidation 
to  allow  its  isolation.  Ainong  t?ie  products  isolated  after  ex- 
posing the  reaction  mixture  to  the  air  were  the  aldeh3''de,  di- 
phenj^larsine  oxide,  and  diphenylarsinic  acid. 


I 


( 

/ 


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I 


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J.;  V ■’ 


PART  III 

Miscellaneous  React-ions. 


-55- 


TKEORKTICAL 


111  order  to  prepare  areenic-euGs-citut  ed  aliphatic  acids 
various  iiiethods  of  synthesis  were  attempted  before  it  was  fouxid 
cnat  the  keyer  reaction  waa  applicaole  for  tnat  synthesis. 

Tne  malonic  ester  sj^nthesis  was  the  first  to  be  considered. 
It  was  hoped  that  an  alJQ'-larsine  group  could  be  introduced  i/ito 
the  malonic  ester  by  means  of  aikyl  chloroarsine  in  the  same 
way  as  an  alkyl  group  b}^  an  alkyl  halide.  The  expected  reac- 
tion; 

COOC3H6  COOC2HB  COOH 

CHs  + Na(  C4Hp  )3AsC1  — >CHAs(  C4H9  )s  — ^CHAs(  C4H9  > 

COOCaHn  COOCsHb  COOH 

( C4H9  )2AsCH3C00H 

did  not  materialize.  Instead  of  actiiig  like  an  alkyl  halide, 
the  di butylarsine  chloride  was  simply  hydrolj-zed  to  tne  corres- 
ponding arsine  oxide  which  on  long  exposure  to  air  oxialzed  to 
dibutylarsinic  acid. 

The  possibility  of  utilizing  diazoacetic  ester  v^as  next  in- 
vestigated. Judging  from  analogous  reactions  of  diazoacetic 
ester,  the  follovving  reactioii  seemed  probable: 

CH3ASCI3  + H3CHCOOC3H5 CH3As( CHCICOOC2H6  )3  + R3 

The  results,  however,  were  negative.  Although  a reaction  occur- 
red as  indicated  by  the  evolution  of  nitrogen,  onl.y  gummy  pro- 
ducts, for  which  no  method  of  purification  could  be  found,  v/ere 
obtained.  Ko  reaction  occurred  when  secondary  chloroarsizies 
were  used. 

Since  the  chloroarsiiies  gave  unsatisfact ory  results  it  v;as 


f 


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-56- 


thought  that  perhaps  tne  arsines  themselves  might  react  ?>^ith  the 
diazoacetic  ester  to  give  the  desired  arsenic -su'ostituted  acetic 
acid  as  indicated  by  the  following  equations: 

CeHsAsHa  + i^aCHCOOCaHs CeH6As(  CHa COOCaHs  )a  + ha 

(CeHB)aAsE  + haCHCOOCaHB ( CeHs  )aAsCH3C00H  + ha 

A reaction  occurred  wii-h  both  pri/i;ary  and  v/ith  secondary 
arsine  as  iiidicated  by  tne  brisk  evolutioxi  of  nitrogen,  out  the 
difficulty  arose  in  tne  isolation  of  tne  products.  In  the  case 
of  diphexiylarsiiie , the  resulting  product  was  unstable  axid  imme- 
diatel5''  oxidized  giving  diphei]5’’larsiiiic  acid  instead  of  the  de- 
sired product.  With  pheiiylarsine  an  oil  was  obtained  v/hicn 
could. .not  be  distilled  evexi  under  reduced  pressure  vtfithout  de- 
composition. Saponification  of  the  ester,  instead  of  giviiig  the 
desired  acid,  gave  pheii3'’larsine  oxide,  indicating  that  the  alka- 
li used  hydrolyzed  the  compouiid  betweexi  che  arsinic  and  acetic 
acid  groups.  In  view  of  the  fact  bhc^t  this  prelimixiary  work  did 
not  look  promising,  and  that  the  starting  materials  were  diffi- 
cult to  prepare  in  large  amounts,  the  work  was  abandoned  at  this 
point. 

Another  possible  rnetiiod  for  s3^nthesising  an  arsinic-acetic 
acid  derivative  was  seexi  in  the  condexisatioxi  of  ethyl  chloro- 
acetate  with  a chloro-arsine  by  means  of  a metal  sucn  as  sodium 
or  magnesium.  It  was  sooxi  found  that  the  latter  did  xiot  cause 
an.y  condensation,  while  the  former  produced  a mixture  of  guimgy 
products. 

A reactioxi  whicn  appeared  to  be  the  most  promising  was  tnat 


-57- 


between  the  Grignard  reagent  and  pheiiylarsine . The  equation  is 
as  follov/s: 

CHsMgl  + CsHbAsHs > CH4  + CeHeAsC iiigl  )a 

This  reaction  went  very  sniooth;ly,  and  it  seems  quite  feasible 
that  the  product  formed  could  be  converted  to  an  acetic  acid 
derivative  by  treatment  with  ethyl  chloroacetat e as  indicated 
by  the  equation: 

CeH6As(MgI)3  + CICH3COOC3K6 CrHbAsC CH3COOC3E6  )3+kgClI 

Since  the  desired  type  of  compound  could  be  readily  synthesized 
by  the  Meyer  reaction,  further  work  was  discontinued,  Neverthe- 
less, this  latter  reaction  of  the  arsines  is  not  only  interest- 
ing, but  may  be  useful  in  the  synthesis  of  certain  types  of 
compounds » 


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^8- 


E^PEHIi/lSlTTAL 

Alkviarsine  cnlor ide  on  sodium-malonic  ester* 

The  ordinary  procedure  for  a njaionic  ester  synthesis  was 
followed.  1.5  g.  of  sliced  sodium  was  added  gradually  to  I3  cc. 
of  absolute  alcohol.  When  all  had  gone  iiibo  solution,  10. 7 g. 
oi‘  freshly  distilled  ethyl  malonate  was  alowly  added,  and  this 
followed  by  15  g.  of  basic  di'outylarsine  chloride  . The  mixture 
was  refluxed  for  five  hours,  the  greater  amount  of  the  alcohol 
distilled  off,  the  residue  poured  into  ice  water,  and  then  ex- 
tracted with  ether.  The  ether  was  allowed  to  evaporate  spontan- 
eously, and  at  the  end  of  tv;o  weeks  a crystalline  mass  mixed 
with  a very  tarry  riiateriax  remairied.  The  crystals  were  filtered 
off,  and  the  adiiering  tar  carefull3'-  washed  off  with  ether.  The 
product  thus  obtained  melted  correctly  for  dibutylarsinic  acid. 

A yield  of  7 8^*  of  the  same  were  obtained.  There  was  no  indica- 
tion of  the  presence  of  the  desired  dibuty larsinic-malonic  ester. 
piazQ-acet  ic  ester  on  Ars  i^ies  . 

Ethyl  diazQ  acetate . This  compound  was  prepared  from  glyco- 
coll  ester  hyaro chloride  '03?^  Silberrad's  modification  of  the 
Curtius  method  with  satisfactory  results.  (-40} 

Diazo-acetic  ester  and  Me thvlars ine  dichloride . To  a solu- 
tion of  24  g.  of  diazo-acetic  ester  in  25  cc.  of  petroleum  ether, 
9 cc.  of  methylarsine  dichloride  were  gradually  added.  A brisk 
reaction  set  in  immediately  as  indicated  by  the  evolution  of 
nitrogen.  A white  precipitate  soon  began  to  separate  out,  but 
in  the  course  of  an  hour  it  became  gummy  and  finally  turned  to 


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-59- 

an  oil  insoluble  in  the  solvent  used*  ITie  reaction  was  complete 
in  about  3 hours.  Al’ter  removing  the  petroleum  ether,  13  B*  of 
a dark  pitch-like  substance  remained  vniich  could  noo  oe  distill- 
ed even  under  diminished  pressure  wiuhoui.  decomposition.  It 
was  saponified  by  refluxing  with  ^0  cc.  of  10  per  cent  sodium 
nydroxide  solution.  On  acidification,  there  was  no  precipitate, 
however,  and  no  acid  could  be  isolated. 

Diazo-acet ic  ester  with  Diphenv lar s ine . The  reaction  was 
carried  out  in  a small  flask  fitted  with  a reflux  condenser  and 
a dropping  funnel.  A slow  stream  of  dry  carbon  dioxide  was 
passed  through  the  apparatus  while  14. S cc.  of  ethyl-diazo- 
acetate were  added  dropwise  to  32  g.  of  aiphenj^'l-a-rsine . On 
slight  warmirig  a steady  evolution  of  nitrogen  set  iii,  ana  in 
the  course  of  a naif  hour,  the  reaction  was  over.  As  soon  as 
the  reaction  mixture  was  exposed  to  the  air,  oxidation  took 
place  as  shown  by  the  evolution  of  heat.  In  a short  time  di- 
phenylarsinic  acid  began  to  separate  out  and  v/as  the  main  pro- 
duct. No  other  compound  appeared  to  be  present  in  any  apprecia- 
ble amount  s . 

Diaz o-acetic  ester  with  Phenvlarsine.  Tne  reaction  was 
carried  out  in  the  same  manner  as  in  the  preceding  experiment. 

28  g.  of  diazo-acetic  ester  were  slowly  added  to  23  g.  of  phenyl- 
arsine.  An  immediate  but  moderate  reaction  set  in  wriich  continu- 
ed about  four  hours.  V/]ien  tne  reaction  was  completed  on  the 
water  bath  a brisk  evolution  of  nitrogen  occurred.  At  the  end 
of  13  minutes  iieither  ethyl  aiazo-acetate , nor  free  phexiylar- 


1 


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-60- 

sine  remained.  About  30  g*  of  oil  wab  obtained  whic]^  since  it 
could  not  be  distilled  v,/ithout  dec omposi bi oii^ was  saponified  oy 
means  of  a 10  per  cent  sodium  hydroxide  solution.  After  reflux- 
ing for  3 hours  all  went  into  solution.  On  rendering  tne  solu- 
tion acid,  a gummj''  substance  separated  whic'n  on  standing?  hard- 
ened to  a granular  macs.  About  10  g.  of  material  were  obtained. 
After  recrystallization  from  chloroform,  the  product  vi^as  iden- 
tified as  phei]ylarsine  oxide.  There  was  no  iiidication  of  the 
desired  acetic  acid  derivative. 

Grignard  Reagent  on  Arsines . 

Gr jgnard  Reagent  on  Pnenvlarsine . Tne  Grignard  reagent  was 
prepared  in  the  usual  manner  by  adding:  20  g.  of  methyl  iodide 
to  3*3  of  finely’"  divided  magnesium  covered  with  100  cc.  of 
drj^  ebher.  The  main  reaction  was  carried  out  in  a liter  flask 
fitted  with  a small  dropping  funnel  ana  a reflux  condenser  to 
which  a delivery  tube  extending  into  a basin  of  water  w-as  at- 
tached. The  liberated  methane  was  collected  over  water  in  a 
graduated  flask. 

0 

Subs.  3 S*  phenylarsine  1042  cc.  metnane  at  24  743  mm. 

0 

Calc.  vol.  for  methane  at  0 760  rmn.  : 93S  cc.  Found:  906cc 


n -r-  ^ti  rarsm 


-6i- 


SUMviARY 

An  attempt  to  introduce  aii  alkyiarsine  group  into  maloiiic 
eJBter  in  the  same  way  that  alkyl  groups  are  iiitroduced , Tailed, 
the  alkyl-arsine  chloride  merel3^  Deiiig  hydrolysing  to  the  cor- 
responding oxide. 

An  attempt  to  prepare  arsenic-suosti wUt ed  acetic  acid  cy 
cue  action  of  diazoacetic  ester  On  jaeth3''ldichlor oarsine  result- 
ed ii*  tarr3?-  products  which  could  not  oe  purified. 

A siiiiilar  attempt  using  diazoacetic  ester  on  phen3^1arsine 
failed.  Although  a reaction  took  place,  the  desirea  product 
could  xiot  be  isolated. 

Unsatisf actory  resulus  were  also  obtained  w'hen  dizao- 
acetic  ester  reacted  with  diphen3a- arsine.  The  product  formed 
was  too  sensitive  to  oxidation  to  allow  its  isolawion. 

Phenylarsine  reacts  v/ith  the  Grignard  reagent  analogously 
to  aniline  giving  off  a,  h3^drocarbon  in  the  theoretical  amount. 


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BIBLIOaHAPHY. 


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10.  Pehn  and  Mleox,  Am.Chem.J.,  33,  129  (1905) 

11.  Eihbert,  Ber.  , 3^,  160  (190"^ 

12.  Auger  and  Billy,  Gompt.rend.,  139  , 597  (1904) 

15.  Baeyer,  Annalen,  107 , 282  (1856) 

14.  Gahours,  Gompt.rend.,  1023  (i860) 

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YITA 

The  ’;7riter  was  horn  at  Theresa,  ’Wisconsin,  July  18,  1894.  He 
completed  his  elementary  school  course  in  that  village,  and  was 
graduated  from  the  liadison  (’Yisconsin)  High  School  in  1914.  The 
following  fall  he  entered  the  Univeisitj;  of  'Yisconsin  Irom  which 
institution  he  received  the  degree  of  Bacheloi  of  Science  in 
Ghemistrj',  June  1918,  and  the  degree  of  Haster  of  Science,  June 
1919.  After  teaching  at  Vanderbilt  University  for  one  year,  he 
entered  the  University  of  Illinois  in  the  summer  of  19 2C,  holding 
a fellowship  for  the  year  192C-E1. 

Appointments : 

Assistant  University  of  Wisconsin  1918-19 

Instructor  Vanderbilt  University  1919-20 

Fellow  University  of  Illinois.  1920-21 

Publications ; 

The  Preparation  of  p-Phenylenediamine  and  Aniline  from 
Their  Corresponding  Chlorobenzenes.  By  Armand  J.  Quick. 

J .Am.Chera.Soc. , 42,  1033  (1920) 

The  Properties  of  Subsidiary  Valence  Croups.  I.  The  vlole- 
cular  Volum.e  Pielat ionships  of  the  Hydrates  and  Ammines 
of  Some  Cobalt  Compounds.  II.  Subsidiary  Croup  Mobility 
as  Studied  by  the  Heat  Decomposition  of  Some  Cobalt- 
amraines.  By  George  L, Clark,  A.J.  Quick,  and  7/illiam  D. 
Harkins.  J . Am .Chem.E oc . , 42,  2483  (1920) 


